Is IFT27 p.Ala142Val (c.425C>T) pathogenic?

IFT27 p.Ala142Val (c.425C>T) is classified Benign in IFT27 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-02). AlphaMissense: likely pathogenic (0.752); Low-frequency (popmax 2.92%, afr).

How common is IFT27 p.Ala142Val (c.425C>T) in the general population?

IFT27 p.Ala142Val (c.425C>T) is low-frequency (popmax 2.92%, afr) (gnomAD).

What do computational predictors say about IFT27 p.Ala142Val (c.425C>T)?

AlphaMissense predicts likely pathogenic (score 0.752) — an in-silico prediction, not a clinical call.

IFT27 p.Ala142Val

c.425C>T · rs78099126 · VCV786380

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.752 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.92%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.752	likely pathogenic
REVEL	0.831	moderately pathogenic-leaning
SaProt	LLR -14.64	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 17 kb · p 0.13 · 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 2.92% African / African-American · 2,177/74,638 alleles

Filtering AF 2.81% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.77%

Overall 0.157% 2,503/1,595,016 alleles · low-frequency exomes 1,276/1,442,658 · genomes 1,227/152,358 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.92%	34
Remaining individualsnot grpmax-eligible	0.219%	457
Middle Eastern	0.166%	601
Admixed American	0.155%	645
South Asian	0.0216%	4,626
East Asian	0.00906%	11,032
European (non-Finnish)	0.00565%	17,692
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,494

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: IFT27
Protein: p.Ala142Val
Coding: c.425C>T
MANE Select: NM_001177701
dbSNP: rs78099126
Type: single nucleotide variant
Location: chr22:36762941 (GRCh38)

Full IFT27 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/ift27-p-ala142val (accessed [today's date]).

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