Is BORCS5 p.Arg45Gln (c.134G>A) pathogenic?

BORCS5 p.Arg45Gln (c.134G>A) is classified Uncertain significance in BORCS5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). AlphaMissense: likely benign (0.2229); Very rare (popmax 0.00246%, nfe).

How common is BORCS5 p.Arg45Gln (c.134G>A) in the general population?

BORCS5 p.Arg45Gln (c.134G>A) is very rare (popmax 0.00246%, nfe) (gnomAD).

What do computational predictors say about BORCS5 p.Arg45Gln (c.134G>A)?

AlphaMissense predicts likely benign (score 0.2229) — an in-silico prediction, not a clinical call.

BORCS5 p.Arg45Gln

c.134G>A · rs144877374 · VCV2458247

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2229 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00246%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2229	likely benign
REVEL	0.246	benign-leaning
SaProt	LLR -6.48	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 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 108 kb · p 0.7 · regional, not allelic
Overall
CADD	24.1	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 0.00246% European (non-Finnish) · 29/1,180,030 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00991% 160/1,614,020 alleles · very rare exomes 143/1,461,884 · genomes 17/152,136 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.348%	287
Remaining individualsnot grpmax-eligible	0.0384%	2,604
European (non-Finnish)grpmax	0.00246%	40,691
South Asian	0.0022%	45,543
Admixed American	0.00167%	59,984
African / African-American	0.00133%	74,920

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg45Gln
Coding: c.134G>A
MANE Select: NM_058169
dbSNP: rs144877374
Type: single nucleotide variant
Location: chr12:12361281 (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-arg45gln (accessed [today's date]).

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