Is IFT74 p.Arg70His (c.209G>A) pathogenic?

IFT74 p.Arg70His (c.209G>A) is classified Uncertain significance in IFT74 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-15). AlphaMissense: ambiguous (0.5016); Very rare (popmax 0.00502%, amr).

How common is IFT74 p.Arg70His (c.209G>A) in the general population?

IFT74 p.Arg70His (c.209G>A) is very rare (popmax 0.00502%, amr) (gnomAD).

What do computational predictors say about IFT74 p.Arg70His (c.209G>A)?

AlphaMissense predicts ambiguous (score 0.5016) — an in-silico prediction, not a clinical call.

IFT74 p.Arg70His

c.209G>A · rs1424717476 · VCV1979876

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5016 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00502%, amr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5016	ambiguous
REVEL	0.709	pathogenic-leaning
SaProt	LLR -10.80	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 101 kb · p 1.9e-05 · regional, not allelic
Overall
CADD	31.0	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 0.00502% Admixed American · 3/59,770 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000669%

Overall 0.00124% 20/1,613,482 alleles · very rare exomes 20/1,461,222 · genomes 0/152,260 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00502%	19,923
Remaining individualsnot grpmax-eligible	0.0032%	31,234
European (non-Finnish)	0.00127%	78,656

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.Arg70His
Coding: c.209G>A
MANE Select: NM_025103
dbSNP: rs1424717476
Type: single nucleotide variant
Location: chr9:26978216 (GRCh38)
Gene constraint: LOEUF 1.508 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.21
Residue 70: the 'basic region' region; a UniProt-annotated variant site (in jbts40)

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

Similar variants

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IFT74 p.Glu120Ter Pathogenic/Likely pathogenic ★★ same type
IFT74 p.Glu285Ter Pathogenic/Likely pathogenic ★★ same type
IFT74 p.Ala196Val Uncertain significance ★★ ⚠ same type
IFT74 p.Ala558Val Uncertain significance ★★ ⚠ same type
IFT74 p.Arg182Gln Uncertain significance ★★ ⚠ same type
IFT74 p.Arg402Gly Uncertain significance ★★ ⚠ same type

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-arg70his (accessed [today's date]).

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