Is DEFB113 p.Pro44Leu (c.131C>T) pathogenic?

DEFB113 p.Pro44Leu (c.131C>T) is classified Uncertain significance in DEFB113 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-26). AlphaMissense: likely benign (0.1029); Ultra-rare (popmax 0.0243%, afr).

How common is DEFB113 p.Pro44Leu (c.131C>T) in the general population?

DEFB113 p.Pro44Leu (c.131C>T) is ultra-rare (popmax 0.0243%, afr) (gnomAD).

What do computational predictors say about DEFB113 p.Pro44Leu (c.131C>T)?

AlphaMissense predicts likely benign (score 0.1029) — an in-silico prediction, not a clinical call.

DEFB113 p.Pro44Leu

c.131C>T · rs201224982 · VCV2514488

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1029 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0243%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1029	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -6.36	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 1.9	GERP -0.45, phastCons 0.46
Regional constraint	o/e 1.27	unconstrained · MANE · 945 bp · p 0.0073 · regional, not allelic
Overall
CADD	12.47	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 0.0243% African / African-American · 18/74,050 alleles

Filtering AF 0.0156% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.013%

Overall 0.00611% 98/1,604,232 alleles · ultra-rare exomes 91/1,453,314 · genomes 7/150,918 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0243%	4,114
Remaining individualsnot grpmax-eligible	0.0113%	8,857
European (non-Finnish)	0.00596%	16,789
Finnishnot grpmax-eligible	0.00313%	31,913
Admixed American	0.0017%	58,776

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: DEFB113
Protein: p.Pro44Leu
Coding: c.131C>T
MANE Select: NM_001037729
dbSNP: rs201224982
Type: single nucleotide variant
Location: chr6:49968795 (GRCh38)
Gene constraint: LOEUF 1.962 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.43

Full DEFB113 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DEFB113 p.Pro44Thr Likely benign ★ same residue
DEFB113 p.Arg39His Uncertain significance ★ ⚠ same type
DEFB113 p.Cys42Trp Uncertain significance ★ ⚠ same type
DEFB113 p.Cys46Ser Uncertain significance ★ ⚠ same type
DEFB113 p.Cys56Phe Uncertain significance ★ same type
DEFB113 p.His80Gln Uncertain significance ★ ⚠ same type
DEFB113 p.Ile6Leu Uncertain significance ★ ⚠ same type
DEFB113 p.Leu4Ile 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/defb113-p-pro44leu (accessed [today's date]).

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