Is DEFB1 p.Ser32Cys (c.95C>G) pathogenic?

DEFB1 p.Ser32Cys (c.95C>G) is classified Uncertain significance in DEFB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). AlphaMissense: likely pathogenic (0.8329); Ultra-rare (popmax 0.0913%, eas).

How common is DEFB1 p.Ser32Cys (c.95C>G) in the general population?

DEFB1 p.Ser32Cys (c.95C>G) is ultra-rare (popmax 0.0913%, eas) (gnomAD).

What do computational predictors say about DEFB1 p.Ser32Cys (c.95C>G)?

AlphaMissense predicts likely pathogenic (score 0.8329) — an in-silico prediction, not a clinical call.

DEFB1 p.Ser32Cys

c.95C>G · rs569413649 · VCV2519814

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8329 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0913%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8329	likely pathogenic
REVEL	0.121	moderately benign-leaning
SaProt	LLR -11.60	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 -0.29	GERP -3.3
Regional constraint	o/e 2.11	unconstrained · MANE · 7,173 bp · p 2.7e-22 · regional, not allelic
Overall
CADD	20.9	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 0.0913% East Asian · 41/44,888 alleles

Filtering AF 0.0692% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0614%

Overall 0.00291% 47/1,614,096 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0913%	1,095
Remaining individualsnot grpmax-eligible	0.0032%	31,252
Admixed American	0.00167%	60,000
European (non-Finnish)	0.000254%	393,335

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: DEFB1
Protein: p.Ser32Cys
Coding: c.95C>G
MANE Select: NM_005218
dbSNP: rs569413649
Type: single nucleotide variant
Location: chr8:6870793 (GRCh38)
Gene constraint: LOEUF 1.969 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.82 · 15 PDB

Full DEFB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DEFB1 p.Gly27= Benign ★★ same type
DEFB1 p.Ala19Thr Uncertain significance ★ ⚠ same type
DEFB1 p.Ala64Gly Uncertain significance ★ ⚠ same type
DEFB1 p.Asp33Gly Uncertain significance ★ ⚠ same type
DEFB1 p.Cys12Phe Uncertain significance ★ ⚠ same type
DEFB1 p.Cys44Tyr Uncertain significance ★ ⚠ same type
DEFB1 p.Cys59Tyr Uncertain significance ★ ⚠ same type
DEFB1 p.Gly57Ala 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/defb1-p-ser32cys (accessed [today's date]).

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