Is BORCS5 p.Val107Ile (c.319G>A) pathogenic?

BORCS5 p.Val107Ile (c.319G>A) is classified Uncertain significance in BORCS5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-07). AlphaMissense: ambiguous (0.3411); Very rare (popmax 0.00892%, eas).

How common is BORCS5 p.Val107Ile (c.319G>A) in the general population?

BORCS5 p.Val107Ile (c.319G>A) is very rare (popmax 0.00892%, eas) (gnomAD).

What do computational predictors say about BORCS5 p.Val107Ile (c.319G>A)?

AlphaMissense predicts ambiguous (score 0.3411) — an in-silico prediction, not a clinical call.

BORCS5 p.Val107Ile

c.319G>A · VCV3825109

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3411 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3411	ambiguous
REVEL	0.251	benign-leaning
SaProt	LLR -6.61	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 108 kb · p 0.7 · regional, not allelic
Overall
CADD	26.8	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 0.00892% East Asian · 4/44,858 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.00143% 23/1,613,844 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,214
African / African-American	0.00799%	12,508
Admixed American	0.00667%	14,987
South Asian	0.0033%	30,339
European (non-Finnish)	0.000509%	196,645

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: BORCS5
Protein: p.Val107Ile
Coding: c.319G>A
MANE Select: NM_058169
Type: single nucleotide variant
Location: chr12:12435744 (GRCh38)
Gene constraint: LOEUF 1.105 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.54

Full BORCS5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BORCS5 p.Ala154Thr Uncertain significance ★ ⚠ same type
BORCS5 p.Ala79Asp Uncertain significance ★ ⚠ same type
BORCS5 p.Arg157His Uncertain significance ★ ⚠ same type
BORCS5 p.Arg158His Uncertain significance ★ ⚠ same type
BORCS5 p.Arg182Gln Uncertain significance ★ ⚠ same type
BORCS5 p.Arg182Trp Uncertain significance ★ ⚠ same type
BORCS5 p.Arg192Cys Uncertain significance ★ ⚠ same type
BORCS5 p.Arg192His 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/borcs5-p-val107ile (accessed [today's date]).

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