Is DEFB110 p.Arg32Lys (c.95G>A) pathogenic?

DEFB110 p.Arg32Lys (c.95G>A) is classified Uncertain significance in DEFB110 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-30). AlphaMissense: likely benign (0.179); Very rare (popmax 0.0011%, sas).

How common is DEFB110 p.Arg32Lys (c.95G>A) in the general population?

DEFB110 p.Arg32Lys (c.95G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about DEFB110 p.Arg32Lys (c.95G>A)?

AlphaMissense predicts likely benign (score 0.179) — an in-silico prediction, not a clinical call.

DEFB110 p.Arg32Lys

c.95G>A · VCV3271453

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.179 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.179	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -6.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.65	GERP 0.49, phastCons 0.011
Regional constraint	o/e 1.25	unconstrained · MANE · 2,955 bp · p 0.032 · regional, not allelic
Overall
CADD	14.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0011% South Asian · 1/91,016 alleles

Overall 0.000137% 2/1,460,914 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,016
European (non-Finnish)	8.48e-05%	1,179,352

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: DEFB110
Protein: p.Arg32Lys
Coding: c.95G>A
MANE Select: NM_001037497
Type: single nucleotide variant
Location: chr6:50019086 (GRCh38)
Gene constraint: LOEUF 1.95 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.43

Full DEFB110 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DEFB110 p.Ala19Val Uncertain significance ★ ⚠ same type
DEFB110 p.Arg52Lys Uncertain significance ★ ⚠ same type
DEFB110 p.Asn49Ile Uncertain significance ★ ⚠ same type
DEFB110 p.Glu34Gln Uncertain significance ★ ⚠ same type
DEFB110 p.His11Pro Uncertain significance ★ ⚠ same type
DEFB110 p.Leu5Ile Uncertain significance ★ ⚠ same type
DEFB110 p.Lys21Asn Uncertain significance ★ ⚠ same type
DEFB110 p.Phe12Tyr 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/defb110-p-arg32lys (accessed [today's date]).

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