Is LYN p.Asp66Val (c.197A>T) pathogenic?

LYN p.Asp66Val (c.197A>T) is classified Uncertain significance in LYN (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.0946); Ultra-rare (popmax 0.0251%, nfe).

How common is LYN p.Asp66Val (c.197A>T) in the general population?

LYN p.Asp66Val (c.197A>T) is ultra-rare (popmax 0.0251%, nfe) (gnomAD).

What do computational predictors say about LYN p.Asp66Val (c.197A>T)?

AlphaMissense predicts likely benign (score 0.0946) — an in-silico prediction, not a clinical call.

LYN p.Asp66Val

c.197A>T · rs763145713 · VCV1500244

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0946 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0251%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0946	likely benign
REVEL	0.248	benign-leaning
SaProt	LLR -4.89	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 10 kb · p 0.0091 · regional, not allelic
Overall
CADD	21.6	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 0.0251% European (non-Finnish) · 296/1,178,816 alleles

Filtering AF 0.0228% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0218%

Overall 0.0187% 302/1,612,726 alleles · ultra-rare exomes 292/1,460,510 · genomes 10/152,216 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0251%	3,982
African / African-American	0.00534%	18,730
Remaining individualsnot grpmax-eligible	0.0032%	31,222

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.Asp66Val
Coding: c.197A>T
MANE Select: NM_002350
dbSNP: rs763145713
Type: single nucleotide variant
Location: chr8:55947636 (GRCh38)
Gene constraint: LOEUF 0.282 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.44 · 6 PDB
Residue 66: the sh3 domain

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-asp66val (accessed [today's date]).

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