Is BORCS5 p.Pro168Ser (c.502C>T) pathogenic?

BORCS5 p.Pro168Ser (c.502C>T) is classified Uncertain significance in BORCS5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-13). AlphaMissense: likely pathogenic (0.5696); Very rare (popmax 0.00934%, afr).

How common is BORCS5 p.Pro168Ser (c.502C>T) in the general population?

BORCS5 p.Pro168Ser (c.502C>T) is very rare (popmax 0.00934%, afr) (gnomAD).

What do computational predictors say about BORCS5 p.Pro168Ser (c.502C>T)?

AlphaMissense predicts likely pathogenic (score 0.5696) — an in-silico prediction, not a clinical call.

BORCS5 p.Pro168Ser

c.502C>T · rs746646136 · VCV2295434

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5696 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00934%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5696	likely pathogenic
REVEL	0.244	benign-leaning
SaProt	LLR -13.39	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 108 kb · p 0.7 · regional, not allelic
Overall
CADD	27.0	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 0.00934% African / African-American · 7/74,950 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00192% 31/1,614,126 alleles · very rare exomes 30/1,461,874 · genomes 1/152,252 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00934%	10,707
European (non-Finnish)	0.00195%	51,306
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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.Pro168Ser
Coding: c.502C>T
MANE Select: NM_058169
dbSNP: rs746646136
Type: single nucleotide variant
Location: chr12:12465687 (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-pro168ser (accessed [today's date]).

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