Is IFT57 p.Val28Ala (c.83T>C) pathogenic?

IFT57 p.Val28Ala (c.83T>C) is classified Likely benign in IFT57 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-05). AlphaMissense: likely benign (0.0604); Absent from gnomAD v4.1.

How common is IFT57 p.Val28Ala (c.83T>C) in the general population?

IFT57 p.Val28Ala (c.83T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IFT57 p.Val28Ala (c.83T>C)?

AlphaMissense predicts likely benign (score 0.0604) — an in-silico prediction, not a clinical call.

IFT57 p.Val28Ala

c.83T>C · rs2472180227 · VCV2556612

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0604 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0604	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -5.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.23	GERP -4.6
Regional constraint	o/e 0.90	unconstrained · MANE · 60 kb · p 0.023 · regional, not allelic
Overall
CADD	1.892	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: IFT57
Protein: p.Val28Ala
Coding: c.83T>C
MANE Select: NM_018010
dbSNP: rs2472180227
Type: single nucleotide variant
Location: chr3:108222240 (GRCh38)
Gene constraint: LOEUF 1.425 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.92

Full IFT57 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IFT57 c.585+3A>G Likely pathogenic ★★ same type
IFT57 c.981+4A>G Uncertain significance ★★ same type
IFT57 p.Ala155Thr Uncertain significance ★★ ⚠ same type
IFT57 p.Ala37Val Uncertain significance ★★ ⚠ same type
IFT57 p.Arg245Cys Uncertain significance ★★ ⚠ same type
IFT57 p.Asp110Ala Uncertain significance ★★ ⚠ same type
IFT57 p.Asp219His Uncertain significance ★★ ⚠ same type
IFT57 p.Asp228His 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/ift57-p-val28ala (accessed [today's date]).

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