Is IFT74 p.Lys85Arg (c.254A>G) pathogenic?

IFT74 p.Lys85Arg (c.254A>G) is classified Benign in IFT74 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0686); Common (popmax 66.9%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Bardet-Biedl syndrome 22.

What condition is associated with IFT74 p.Lys85Arg (c.254A>G)?

IFT74 p.Lys85Arg (c.254A>G) is associated with Bardet-Biedl syndrome 22 (ClinVar).

How is Bardet-Biedl syndrome inherited?

Typically Autosomal recessive, Oligogenic (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about IFT74 p.Lys85Arg (c.254A>G)?

AlphaMissense predicts likely benign (score 0.0686) — an in-silico prediction, not a clinical call.

IFT74 p.Lys85Arg

Q: How common is IFT74 p.Lys85Arg (c.254A>G) in the general population?

IFT74 p.Lys85Arg (c.254A>G) is common (popmax 66.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.254A>G · rs11555693 · VCV1265179

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0686 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 66.9%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Bardet-Biedl syndrome 22

Computational evidence

Protein change
AlphaMissense	0.0686	likely benign
REVEL	0.178	moderately benign-leaning
SaProt	LLR -6.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 101 kb · p 1.9e-05 · regional, not allelic
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 66.9% East Asian · 29,931/44,708 alleles

Filtering AF 66.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 66.1%

Overall 7.98% 128,591/1,611,946 alleles · common exomes 113,016/1,459,728 · genomes 15,575/152,218 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	66.9%	1
Admixed American	20.7%	5
South Asian	13.9%	7
African / African-American	11.1%	9
Finnishnot grpmax-eligible	10.5%	10
Remaining individualsnot grpmax-eligible	9.23%	11
European (non-Finnish)	4.4%	23
Middle Eastern	3.47%	29
Ashkenazi Jewishnot grpmax-eligible	2.69%	37
Amishnot grpmax-eligible	2.41%	41

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: IFT74
Protein: p.Lys85Arg
Coding: c.254A>G
MANE Select: NM_025103
dbSNP: rs11555693
Type: single nucleotide variant
Location: chr9:26978261 (GRCh38)
Gene constraint: LOEUF 1.508 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.21
Residue 85: the 'basic region' region; a UniProt-annotated variant site (in); a UniProt-annotated variant site (in jbts40)

Full IFT74 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Bardet-Biedl syndrome 22 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Bardet-Biedl syndrome (Orphanet):

Inheritance: Autosomal recessive, Oligogenic
Onset: Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Specific population)

Similar variants

IFT74 p.Lys85Ter Pathogenic ★ same residue
LRRC19 p.Val85Ala Uncertain significance ★ ⚠ same residue
IFT74 c.1685-1G>T Pathogenic/Likely pathogenic ★★ same condition
IFT74 p.Glu120Ter Pathogenic/Likely pathogenic ★★ same condition
IFT74 p.Arg448His Uncertain significance ★★ ⚠ same condition
IFT74 p.Ile498Val Uncertain significance ★★ ⚠ same condition
IFT74 p.Ser32Pro Uncertain significance ★★ ⚠ same condition
IFT74 p.Ile55Met Benign ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ift74-p-lys85arg (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown