Is DEFB105B p.Leu72Val (c.214C>G) pathogenic?

DEFB105B p.Leu72Val (c.214C>G) is classified Uncertain significance in DEFB105B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-07). Rare (popmax 0.191%, sas).

How common is DEFB105B p.Leu72Val (c.214C>G) in the general population?

DEFB105B p.Leu72Val (c.214C>G) is rare (popmax 0.191%, sas) (gnomAD).

DEFB105B p.Leu72Val

c.214C>G · rs1370611682 · VCV2507634

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.191%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.009	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.1	GERP 2.5, phastCons 0.003
Overall
CADD	11.35	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.191% South Asian · 32/16,784 alleles

Filtering AF 0.139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.121%

Overall 0.0604% 47/77,820 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.204%	491
South Asiangrpmax	0.191%	524
Remaining individualsnot grpmax-eligible	0.117%	852
European (non-Finnish)	0.0175%	5,712

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DEFB105B
Protein: p.Leu72Val
Coding: c.214C>G
MANE Select: NM_001040703
dbSNP: rs1370611682
Type: single nucleotide variant
Location: chr8:7489528 (GRCh38)
Structure: AlphaFold pLDDT 72.22
Residue 72: a disulfide bond

Full DEFB105B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DEFB105B p.Asp64Asn Uncertain significance ★ same type
DEFB105B p.Cys67Phe Uncertain significance ★ same type
DEFB105B p.Cys67Tyr 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/defb105b-p-leu72val (accessed [today's date]).

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