Is IFT81 p.Gln656Pro (c.1967A>C) pathogenic?

IFT81 p.Gln656Pro (c.1967A>C) is classified Uncertain significance in IFT81 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-07). AlphaMissense: likely benign (0.1291); Very rare (popmax 0.00192%, amr); Associated with Inborn genetic diseases.

What condition is associated with IFT81 p.Gln656Pro (c.1967A>C)?

IFT81 p.Gln656Pro (c.1967A>C) is associated with Inborn genetic diseases (ClinVar).

How common is IFT81 p.Gln656Pro (c.1967A>C) in the general population?

IFT81 p.Gln656Pro (c.1967A>C) is very rare (popmax 0.00192%, amr) (gnomAD).

What do computational predictors say about IFT81 p.Gln656Pro (c.1967A>C)?

AlphaMissense predicts likely benign (score 0.1291) — an in-silico prediction, not a clinical call.

IFT81 p.Gln656Pro

c.1967A>C · rs767006523 · VCV1489076

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1291 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00192%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1291	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -11.26	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 1.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 91 kb · p 0.022 · regional, not allelic
Overall
CADD	21.6	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 0.00192% Admixed American · 1/52,002 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000441% 7/1,586,902 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00192%	52,002
Remaining individualsnot grpmax-eligible	0.00163%	61,186
South Asian	0.00117%	85,638
European (non-Finnish)	0.000341%	293,092

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.Gln656Pro
Coding: c.1967A>C
MANE Select: NM_014055
dbSNP: rs767006523
Type: single nucleotide variant
Location: chr12:110218162 (GRCh38)
Gene constraint: LOEUF 1.054 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.45
Residue 656: a UniProt-annotated variant site (in srtd19)

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.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
IFT81 p.Arg399Leu 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-gln656pro (accessed [today's date]).

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