Is BSDC1 p.Ser418Phe (c.1253C>T) pathogenic?

BSDC1 p.Ser418Phe (c.1253C>T) is classified Uncertain significance in BSDC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-30). AlphaMissense: likely benign (0.1528); Rare (popmax 0.102%, eas).

How common is BSDC1 p.Ser418Phe (c.1253C>T) in the general population?

BSDC1 p.Ser418Phe (c.1253C>T) is rare (popmax 0.102%, eas) (gnomAD).

What do computational predictors say about BSDC1 p.Ser418Phe (c.1253C>T)?

AlphaMissense predicts likely benign (score 0.1528) — an in-silico prediction, not a clinical call.

BSDC1 p.Ser418Phe

c.1253C>T · rs201994378 · VCV2353777

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1528 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.102%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1528	likely benign
REVEL	0.514	indeterminate
SaProt	LLR -10.35	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 28 kb · p 0.0023 · regional, not allelic
Overall
CADD	32.0	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 0.102% East Asian · 46/44,894 alleles

Filtering AF 0.0789% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0706%

Overall 0.0217% 350/1,613,974 alleles · rare exomes 331/1,461,892 · genomes 19/152,082 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.102%	976
Finnishnot grpmax-eligible	0.0359%	2,783
European (non-Finnish)	0.0219%	4,556
Remaining individualsnot grpmax-eligible	0.0176%	5,681
South Asian	0.00549%	18,218
Admixed American	0.005%	19,993
African / African-American	0.00401%	24,963

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.Ser418Phe
Coding: c.1253C>T
MANE Select: NM_018045
dbSNP: rs201994378
Type: single nucleotide variant
Location: chr1:32368454 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.91
Residue 418: a modified residue (phosphoserine)

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-ser418phe (accessed [today's date]).

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