Is BORCS5 p.Arg182Trp (c.544C>T) pathogenic?

BORCS5 p.Arg182Trp (c.544C>T) is classified Uncertain significance in BORCS5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-20). AlphaMissense: ambiguous (0.5395); Rare (popmax 0.312%, eas).

How common is BORCS5 p.Arg182Trp (c.544C>T) in the general population?

BORCS5 p.Arg182Trp (c.544C>T) is rare (popmax 0.312%, eas) (gnomAD).

What do computational predictors say about BORCS5 p.Arg182Trp (c.544C>T)?

AlphaMissense predicts ambiguous (score 0.5395) — an in-silico prediction, not a clinical call.

BORCS5 p.Arg182Trp

c.544C>T · VCV3992396

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5395 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.312%, eas)

Computational evidence

Protein change
AlphaMissense	0.5395	ambiguous
REVEL	0.4	indeterminate
SaProt	LLR -14.74	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.9	GERP -3.4, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 108 kb · p 0.7 · regional, not allelic
Overall
CADD	22.6	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 0.312% East Asian · 140/44,900 alleles

Filtering AF 0.27% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.254%

Overall 0.00973% 157/1,613,940 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.312%	321
Admixed American	0.00333%	30,006
Remaining individualsnot grpmax-eligible	0.0032%	31,242
African / African-American	0.00267%	37,478
South Asian	0.0011%	91,090
European (non-Finnish)	0.000847%	118,004

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.Arg182Trp
Coding: c.544C>T
MANE Select: NM_058169
Type: single nucleotide variant
Location: chr12:12465729 (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.Arg182Gln Uncertain significance ★ ⚠ same residue
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.Arg192Cys Uncertain significance ★ ⚠ same type
BORCS5 p.Arg192His Uncertain significance ★ ⚠ same type
BORCS5 p.Arg45Gln 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-arg182trp (accessed [today's date]).

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