Is BORCS8 p.Val30Met (c.88G>A) pathogenic?

BORCS8 p.Val30Met (c.88G>A) is classified Uncertain significance in BORCS8 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-18). AlphaMissense: likely pathogenic (0.6363); Very rare (popmax 0.00196%, amr).

How common is BORCS8 p.Val30Met (c.88G>A) in the general population?

BORCS8 p.Val30Met (c.88G>A) is very rare (popmax 0.00196%, amr) (gnomAD).

What do computational predictors say about BORCS8 p.Val30Met (c.88G>A)?

AlphaMissense predicts likely pathogenic (score 0.6363) — an in-silico prediction, not a clinical call.

BORCS8 p.Val30Met

c.88G>A · rs1000362990 · VCV2233462

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6363 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00196%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6363	likely pathogenic
REVEL	0.212	benign-leaning
SaProt	LLR -8.20	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.96 · regional, not allelic
Overall
CADD	24.0	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 0.00196% Admixed American · 1/50,944 alleles

Filtering AF 0.0003% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000217%

Overall 0.000645% 10/1,551,180 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00196%	50,944
Remaining individualsnot grpmax-eligible	0.00166%	60,076
European (non-Finnish)	0.000698%	143,364

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: BORCS8
Protein: p.Val30Met
Coding: c.88G>A
MANE Select: NM_001145784
dbSNP: rs1000362990
Type: single nucleotide variant
Location: chr19:19186955 (GRCh38)
Gene constraint: LOEUF 1.104 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.74

Full BORCS8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BORCS8 p.Glu68Ter Likely pathogenic ★ same type
BORCS8 p.Ala25Gly Uncertain significance ★ ⚠ same type
BORCS8 p.Arg40His Uncertain significance ★ ⚠ same type
BORCS8 p.Arg55Cys Uncertain significance ★ ⚠ same type
BORCS8 p.Arg55Leu Uncertain significance ★ ⚠ same type
BORCS8 p.Arg85His Uncertain significance ★ ⚠ same type
BORCS8 p.Arg85Leu Uncertain significance ★ ⚠ same type
BORCS8 p.Arg98Trp 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/borcs8-p-val30met (accessed [today's date]).

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