Is BORCS6 p.Ala91Pro (c.271G>C) pathogenic?

BORCS6 p.Ala91Pro (c.271G>C) is classified Uncertain significance in BORCS6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely benign (0.0679); Ultra-rare (popmax 0.0479%, afr).

How common is BORCS6 p.Ala91Pro (c.271G>C) in the general population?

BORCS6 p.Ala91Pro (c.271G>C) is ultra-rare (popmax 0.0479%, afr) (gnomAD).

What do computational predictors say about BORCS6 p.Ala91Pro (c.271G>C)?

AlphaMissense predicts likely benign (score 0.0679) — an in-silico prediction, not a clinical call.

BORCS6 p.Ala91Pro

c.271G>C · VCV3992401

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0679 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0479%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0679	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -6.17	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 -4.3	GERP -4
Regional constraint	o/e 1.00	unconstrained · MANE · 1,070 bp · p 0.93 · regional, not allelic
Overall
CADD	0.016	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 0.0479% African / African-American · 35/73,110 alleles

Filtering AF 0.0353% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.031%

Overall 0.00252% 39/1,547,528 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0479%	2,089
Admixed American	0.00392%	25,485
Remaining individualsnot grpmax-eligible	0.00333%	30,021

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: BORCS6
Protein: p.Ala91Pro
Coding: c.271G>C
MANE Select: NM_017622
Type: single nucleotide variant
Location: chr17:8189870 (GRCh38)
Gene constraint: LOEUF 1.683 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.53
Residue 91: the 'disordered' region

Full BORCS6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BORCS6 p.Ala244Glu Uncertain significance ★ ⚠ same type
BORCS6 p.Ala244Gly Uncertain significance ★ ⚠ same type
BORCS6 p.Ala285Val Uncertain significance ★ ⚠ same type
BORCS6 p.Ala339Ser Uncertain significance ★ ⚠ same type
BORCS6 p.Arg109Trp Uncertain significance ★ ⚠ same type
BORCS6 p.Arg269Trp Uncertain significance ★ ⚠ same type
BORCS6 p.Arg274Gln Uncertain significance ★ ⚠ same type
BORCS6 p.Arg41Gln 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/borcs6-p-ala91pro (accessed [today's date]).

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