Is FYN p.Val368Ala (c.1103T>C) pathogenic?

FYN p.Val368Ala (c.1103T>C) is classified Uncertain significance in FYN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely pathogenic (0.9489); Absent from gnomAD v4.1.

How common is FYN p.Val368Ala (c.1103T>C) in the general population?

FYN p.Val368Ala (c.1103T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FYN p.Val368Ala (c.1103T>C)?

AlphaMissense predicts likely pathogenic (score 0.9489) — an in-silico prediction, not a clinical call.

FYN p.Val368Ala

c.1103T>C · rs2536568517 · VCV2490777

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9489 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9489	likely pathogenic
REVEL	0.79	moderately pathogenic-leaning
SaProt	LLR -12.99	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.9, phastCons 1
Regional constraint	o/e 0.29	constrained · MANE · 33 kb · p 1.8e-26 · regional, not allelic
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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: FYN
Protein: p.Val368Ala
Coding: c.1103T>C
MANE Select: NM_002037
dbSNP: rs2536568517
Type: single nucleotide variant
Location: chr6:111694644 (GRCh38)
Gene constraint: LOEUF 0.215 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.62 · 53 PDB
Residue 368: the protein kinase domain; an α-helix

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

Similar variants

FYN p.Asp506Glu Benign ★★ same type
FYN c.344+1G>A Uncertain significance ★ same type
FYN p.Ala55Thr Uncertain significance ★ ⚠ same type
FYN p.Arg123Cys Uncertain significance ★ ⚠ same type
FYN p.Arg161Ter Uncertain significance ★ same type
FYN p.Arg29Cys Uncertain significance ★ ⚠ same type
FYN p.Asp8Glu Uncertain significance ★ ⚠ same type
FYN p.Asp92Asn 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/fyn-p-val368ala (accessed [today's date]).

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