Is FYN p.Val63Ile (c.187G>A) pathogenic?

FYN p.Val63Ile (c.187G>A) is classified Uncertain significance in FYN (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-11). AlphaMissense: likely benign (0.0932); Rare (popmax 0.561%, mid).

How common is FYN p.Val63Ile (c.187G>A) in the general population?

FYN p.Val63Ile (c.187G>A) is rare (popmax 0.561%, mid) (gnomAD).

What do computational predictors say about FYN p.Val63Ile (c.187G>A)?

AlphaMissense predicts likely benign (score 0.0932) — an in-silico prediction, not a clinical call.

FYN p.Val63Ile

c.187G>A · rs62620251 · VCV2206524

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0932 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.561%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0932	likely benign
REVEL	0.246	benign-leaning
SaProt	LLR -7.35	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 7.6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 12 kb · p 3.8e-05 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.561% Middle Eastern · 34/6,062 alleles

Filtering AF 0.412% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.361%

Overall 0.0268% 433/1,614,102 alleles · rare exomes 386/1,461,886 · genomes 47/152,216 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.561%	178
Ashkenazi Jewishnot grpmax-eligible	0.128%	779
Admixed American	0.0783%	1,277
South Asian	0.0505%	1,980
Remaining individualsnot grpmax-eligible	0.0368%	2,718
African / African-American	0.0227%	4,413
European (non-Finnish)	0.0192%	5,198
East Asian	0.00223%	44,882

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: FYN
Protein: p.Val63Ile
Coding: c.187G>A
MANE Select: NM_002037
dbSNP: rs62620251
Type: single nucleotide variant
Location: chr6:111719865 (GRCh38)
Gene constraint: LOEUF 0.215 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.62 · 53 PDB

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-val63ile (accessed [today's date]).

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