Is BSDC1 p.Ser12Arg (c.36C>G) pathogenic?

BSDC1 p.Ser12Arg (c.36C>G) is classified Uncertain significance in BSDC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-28). AlphaMissense: likely pathogenic (0.945); Ultra-rare (popmax 0.0133%, afr).

How common is BSDC1 p.Ser12Arg (c.36C>G) in the general population?

BSDC1 p.Ser12Arg (c.36C>G) is ultra-rare (popmax 0.0133%, afr) (gnomAD).

What do computational predictors say about BSDC1 p.Ser12Arg (c.36C>G)?

AlphaMissense predicts likely pathogenic (score 0.945) — an in-silico prediction, not a clinical call.

BSDC1 p.Ser12Arg

c.36C>G · VCV4216436

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.945 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.945	likely pathogenic · top 10% in BSDC1
REVEL	0.316	indeterminate
SaProt	LLR -10.72	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 28 kb · p 0.0023 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0133% African / African-American · 10/74,958 alleles

Filtering AF 0.00722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.000745% 12/1,610,080 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0133%	7,496
East Asian	0.00224%	44,686
Remaining individualsnot grpmax-eligible	0.00161%	62,274

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.Ser12Arg
Coding: c.36C>G
MANE Select: NM_018045
Type: single nucleotide variant
Location: chr1:32394116 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.91

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-ser12arg (accessed [today's date]).

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