Is BSDC1 p.Pro167Ser (c.499C>T) pathogenic?

BSDC1 p.Pro167Ser (c.499C>T) is classified Uncertain significance in BSDC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely benign (0.0919); Ultra-rare (popmax 0.0152%, afr).

How common is BSDC1 p.Pro167Ser (c.499C>T) in the general population?

BSDC1 p.Pro167Ser (c.499C>T) is ultra-rare (popmax 0.0152%, afr) (gnomAD).

What do computational predictors say about BSDC1 p.Pro167Ser (c.499C>T)?

AlphaMissense predicts likely benign (score 0.0919) — an in-silico prediction, not a clinical call.

BSDC1 p.Pro167Ser

c.499C>T · VCV4216438

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0919 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0152%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0919	likely benign
REVEL	0.383	indeterminate
SaProt	LLR -6.88	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 28 kb · p 0.0023 · regional, not allelic
Overall
CADD	26.1	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 0.0152% African / African-American · 11/72,416 alleles

Filtering AF 0.00843% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00653%

Overall 0.00111% 17/1,537,576 alleles · ultra-rare exomes 11/1,385,410 · genomes 6/152,166 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0152%	6,583
Remaining individualsnot grpmax-eligible	0.00675%	14,818
Admixed American	0.00407%	24,549

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: BSDC1
Protein: p.Pro167Ser
Coding: c.499C>T
MANE Select: NM_018045
Type: single nucleotide variant
Location: chr1:32378753 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.91
Residue 167: the bsd domain

Full BSDC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BSDC1 c.190-36C>G Uncertain significance ★ same type
BSDC1 p.Ala145Thr Uncertain significance ★ ⚠ same type
BSDC1 p.Ala145Val Uncertain significance ★ ⚠ same type
BSDC1 p.Ala20Thr Uncertain significance ★ ⚠ same type
BSDC1 p.Ala28Thr Uncertain significance ★ ⚠ same type
BSDC1 p.Ala295Val Uncertain significance ★ ⚠ same type
BSDC1 p.Ala2Val Uncertain significance ★ ⚠ same type
BSDC1 p.Ala411Val 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/bsdc1-p-pro167ser (accessed [today's date]).

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