Is BYSL p.Val262Ile (c.784G>A) pathogenic?

BYSL p.Val262Ile (c.784G>A) is classified Likely benign in BYSL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-10). AlphaMissense: likely benign (0.0569); Ultra-rare (popmax 0.0379%, eas).

How common is BYSL p.Val262Ile (c.784G>A) in the general population?

BYSL p.Val262Ile (c.784G>A) is ultra-rare (popmax 0.0379%, eas) (gnomAD).

What do computational predictors say about BYSL p.Val262Ile (c.784G>A)?

AlphaMissense predicts likely benign (score 0.0569) — an in-silico prediction, not a clinical call.

BYSL p.Val262Ile

c.784G>A · rs143381928 · VCV2387907

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0569 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0379%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0569	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -3.08	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 6.3	GERP 1.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 11 kb · p 0.019 · regional, not allelic
Overall
CADD	15.57	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 0.0379% East Asian · 17/44,884 alleles

Filtering AF 0.0241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00223% 36/1,613,888 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0379%	2,640
Admixed American	0.00833%	11,998
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
Remaining individualsnot grpmax-eligible	0.0016%	62,482
African / African-American	0.00134%	74,882
European (non-Finnish)	0.000932%	107,269

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: BYSL
Protein: p.Val262Ile
Coding: c.784G>A
MANE Select: NM_004053
dbSNP: rs143381928
Type: single nucleotide variant
Location: chr6:41931475 (GRCh38)
Gene constraint: LOEUF 0.632 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 78.24 · 13 PDB
Residue 262: an α-helix

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

Similar variants

MED20 p.Arg26Trp Uncertain significance ★★ ⚠ same type
MED20 p.Met30Val Uncertain significance ★★ ⚠ same type
BYSL p.Ala279Pro Uncertain significance ★ ⚠ same type
BYSL p.Ala28Glu Uncertain significance ★ ⚠ same type
BYSL p.Ala71Gly Uncertain significance ★ ⚠ same type
BYSL p.Arg131His Uncertain significance ★ ⚠ same type
BYSL p.Arg145His Uncertain significance ★ ⚠ same type
BYSL p.Arg189Gln 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/bysl-p-val262ile (accessed [today's date]).

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