Is DEFB1 p.Cys37Ter (c.111C>A) pathogenic?

DEFB1 p.Cys37Ter (c.111C>A) is classified Likely benign in DEFB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-30). Rare (popmax 0.858%, afr).

How common is DEFB1 p.Cys37Ter (c.111C>A) in the general population?

DEFB1 p.Cys37Ter (c.111C>A) is rare (popmax 0.858%, afr) (gnomAD).

DEFB1 p.Cys37Ter

c.111C>A · rs5743490 · VCV712566

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.858%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (2 of 2) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.7	GERP -3.4
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.858% African / African-American · 644/75,050 alleles

Filtering AF 0.803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.781%

Overall 0.0458% 740/1,614,210 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.858%	117
Remaining individualsnot grpmax-eligible	0.04%	2,500
Admixed American	0.0317%	3,159
South Asian	0.00988%	10,120
Finnishnot grpmax-eligible	0.00937%	10,673
European (non-Finnish)	0.00305%	32,779
East Asian	0.00223%	44,892

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.Cys37Ter
Coding: c.111C>A
MANE Select: NM_005218
dbSNP: rs5743490
Type: single nucleotide variant
Location: chr8:6870777 (GRCh38)
Gene constraint: LOEUF 1.969 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.82 · 15 PDB
Residue 37: a disulfide bond; an α-helix

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-cys37ter (accessed [today's date]).

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