Is DEFB108B p.Pro63Gln (c.188C>A) pathogenic?

DEFB108B p.Pro63Gln (c.188C>A) is classified Uncertain significance in DEFB108B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). AlphaMissense: likely benign (0.2209); Ultra-rare (popmax 0.0143%, sas).

How common is DEFB108B p.Pro63Gln (c.188C>A) in the general population?

DEFB108B p.Pro63Gln (c.188C>A) is ultra-rare (popmax 0.0143%, sas) (gnomAD).

What do computational predictors say about DEFB108B p.Pro63Gln (c.188C>A)?

AlphaMissense predicts likely benign (score 0.2209) — an in-silico prediction, not a clinical call.

DEFB108B p.Pro63Gln

c.188C>A · rs775985368 · VCV3081296

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2209 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0143%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2209	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -6.76	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 0.94	GERP 1.5
Regional constraint	o/e 1.15	unconstrained · MANE · 4,359 bp · p 0.16 · regional, not allelic
Overall
CADD	13.52	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 0.0143% South Asian · 13/90,976 alleles

Filtering AF 0.00845% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00662%

Overall 0.00211% 34/1,611,770 alleles · ultra-rare exomes 29/1,459,614 · genomes 5/152,156 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0143%	6,998
African / African-American	0.00401%	24,931
Admixed American	0.00333%	29,994
East Asian	0.00223%	44,902
Remaining individualsnot grpmax-eligible	0.00161%	62,298
European (non-Finnish)	0.00119%	84,273

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: DEFB108B
Protein: p.Pro63Gln
Coding: c.188C>A
MANE Select: NM_001002035
dbSNP: rs775985368
Type: single nucleotide variant
Location: chr11:71837528 (GRCh38)
Gene constraint: LOEUF 1.849 · pLI 0.19 (gnomAD)
Structure: AlphaFold pLDDT 69.15

Full DEFB108B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DEFB108B p.Gln53Arg Benign ★★ same type
DEFB108B p.Ala4Val Uncertain significance ★ ⚠ same type
DEFB108B p.Arg30Cys Uncertain significance ★ ⚠ same type
DEFB108B p.Asn32Asp Uncertain significance ★ ⚠ same type
DEFB108B p.Cys39Tyr Uncertain significance ★ ⚠ same type
DEFB108B p.Ile3Thr Uncertain significance ★ ⚠ same type
DEFB108B p.Lys72Arg Uncertain significance ★ ⚠ same type
DEFB108B p.Phe24Leu 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/defb108b-p-pro63gln (accessed [today's date]).

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