Is BORCS7 p.Glu8Gln (c.22G>C) pathogenic?

BORCS7 p.Glu8Gln (c.22G>C) is classified Uncertain significance in BORCS7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-26). AlphaMissense: likely benign (0.1708); Very rare (popmax 0.00434%, nfe).

How common is BORCS7 p.Glu8Gln (c.22G>C) in the general population?

BORCS7 p.Glu8Gln (c.22G>C) is very rare (popmax 0.00434%, nfe) (gnomAD).

What do computational predictors say about BORCS7 p.Glu8Gln (c.22G>C)?

AlphaMissense predicts likely benign (score 0.1708) — an in-silico prediction, not a clinical call.

BORCS7 p.Glu8Gln

c.22G>C · VCV3992412

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1708 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00434%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1708	likely benign
REVEL	0.131	moderately benign-leaning
SaProt	LLR -8.01	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 9.4	GERP 1.8, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 8,634 bp · p 0.5 · regional, not allelic
Overall
CADD	24.4	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 0.00434% European (non-Finnish) · 51/1,176,122 alleles

Filtering AF 0.00335% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00303%

Overall 0.0033% 53/1,605,378 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00434%	23,061
Finnishnot grpmax-eligible	0.00158%	63,258
South Asian	0.00112%	89,188

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: BORCS7
Protein: p.Glu8Gln
Coding: c.22G>C
MANE Select: NM_001136200
Type: single nucleotide variant
Location: chr10:102854308 (GRCh38)
Gene constraint: LOEUF 1.484 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.84

Full BORCS7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BORCS7 p.Arg44Gln Uncertain significance ★ ⚠ same type
BORCS7 p.Arg44Trp Uncertain significance ★ ⚠ same type
BORCS7 p.Gln10Arg Uncertain significance ★ ⚠ same type
BORCS7 p.Gln84Arg Uncertain significance ★ ⚠ same type
BORCS7 p.Gln88Glu Uncertain significance ★ ⚠ same type
BORCS7 p.Gln98Glu Uncertain significance ★ ⚠ same type
BORCS7 p.Gly5Arg Uncertain significance ★ ⚠ same type
BORCS7 p.His65Tyr 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/borcs7-p-glu8gln (accessed [today's date]).

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