Is LYN p.Val68Ala (c.203T>C) pathogenic?

LYN p.Val68Ala (c.203T>C) is classified Uncertain significance in LYN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-18). AlphaMissense: ambiguous (0.4268); Very rare (popmax 0.000254%, nfe).

How common is LYN p.Val68Ala (c.203T>C) in the general population?

LYN p.Val68Ala (c.203T>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about LYN p.Val68Ala (c.203T>C)?

AlphaMissense predicts ambiguous (score 0.4268) — an in-silico prediction, not a clinical call.

LYN p.Val68Ala

c.203T>C · rs771212623 · VCV1365310

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4268 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4268	ambiguous
REVEL	0.101	moderately benign-leaning
SaProt	LLR -11.53	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 10 kb · p 0.0091 · regional, not allelic
Overall
CADD	23.7	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 0.000254% European (non-Finnish) · 3/1,179,168 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,132 alleles · very rare exomes 1/1,460,886 · genomes 2/152,246 · joint denominator

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: LYN
Protein: p.Val68Ala
Coding: c.203T>C
MANE Select: NM_002350
dbSNP: rs771212623
Type: single nucleotide variant
Location: chr8:55947642 (GRCh38)
Gene constraint: LOEUF 0.282 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.44 · 6 PDB
Residue 68: the sh3 domain; a β-strand

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

Similar variants

LYN p.Ala150Thr Uncertain significance ★★ ⚠ same type
LYN p.Ala70Thr Uncertain significance ★★ ⚠ same type
LYN p.Arg360Trp Uncertain significance ★★ ⚠ same type
LYN p.Glu47Asp Uncertain significance ★★ ⚠ same type
LYN p.Ile227Val Uncertain significance ★★ ⚠ same type
LYN p.Ser333Asn Uncertain significance ★★ same type
LYN p.Thr30Ala Uncertain significance ★★ ⚠ same type
LYN p.Val45Ile 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/lyn-p-val68ala (accessed [today's date]).

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