Is IFT81 p.Ser67Arg (c.201C>A) pathogenic?

IFT81 p.Ser67Arg (c.201C>A) is classified Uncertain significance in IFT81 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-17). AlphaMissense: ambiguous (0.4293); Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with IFT81 p.Ser67Arg (c.201C>A)?

IFT81 p.Ser67Arg (c.201C>A) is associated with Inborn genetic diseases (ClinVar).

How common is IFT81 p.Ser67Arg (c.201C>A) in the general population?

IFT81 p.Ser67Arg (c.201C>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about IFT81 p.Ser67Arg (c.201C>A)?

AlphaMissense predicts ambiguous (score 0.4293) — an in-silico prediction, not a clinical call.

IFT81 p.Ser67Arg

c.201C>A · rs748400822 · VCV1018736

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4293 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4293	ambiguous
REVEL	0.103	moderately benign-leaning
SaProt	LLR -9.39	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 91 kb · p 0.022 · regional, not allelic
Overall
CADD	19.46	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00164%

Overall 0.00223% 36/1,613,240 alleles · ultra-rare exomes 34/1,461,270 · genomes 2/151,970 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
South Asian	0.00439%	22,761
European (non-Finnish)	0.00263%	38,048

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: IFT81
Protein: p.Ser67Arg
Coding: c.201C>A
MANE Select: NM_014055
dbSNP: rs748400822
Type: single nucleotide variant
Location: chr12:110128102 (GRCh38)
Gene constraint: LOEUF 1.054 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.45
Residue 67: the 'ch (calponin-homology)-like region' region

Full IFT81 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

IFT81 p.Ser67Asn Uncertain significance ★ ⚠ same residue
IFT81 p.Ala116Ser Uncertain significance ★★ ⚠ same condition
IFT81 p.Ala253Thr Uncertain significance ★★ ⚠ same condition
IFT81 p.Ala254Ser Uncertain significance ★★ ⚠ same condition
IFT81 p.Ala357Gly Uncertain significance ★★ ⚠ same condition
IFT81 p.Arg213Gln Uncertain significance ★★ same condition
IFT81 p.Arg251Gly Uncertain significance ★★ ⚠ same condition
IFT81 p.Arg353His Uncertain significance ★★ ⚠ 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/ift81-p-ser67arg (accessed [today's date]).

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