Is DEFB115 p.Pro68Ser (c.202C>T) pathogenic?

DEFB115 p.Pro68Ser (c.202C>T) is classified Uncertain significance in DEFB115 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-19). AlphaMissense: likely benign (0.2067); Ultra-rare (popmax 0.0144%, sas).

How common is DEFB115 p.Pro68Ser (c.202C>T) in the general population?

DEFB115 p.Pro68Ser (c.202C>T) is ultra-rare (popmax 0.0144%, sas) (gnomAD).

What do computational predictors say about DEFB115 p.Pro68Ser (c.202C>T)?

AlphaMissense predicts likely benign (score 0.2067) — an in-silico prediction, not a clinical call.

DEFB115 p.Pro68Ser

c.202C>T · rs758826378 · VCV2337063

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2067 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0144%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2067	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -7.36	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 0.065
Regional constraint	o/e 1.44	unconstrained · MANE · 1,965 bp · p 1.2e-05 · regional, not allelic
Overall
CADD	13.22	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 0.0144% South Asian · 13/90,398 alleles

Filtering AF 0.0085% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00666%

Overall 0.000808% 13/1,609,082 alleles · ultra-rare

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: DEFB115
Protein: p.Pro68Ser
Coding: c.202C>T
MANE Select: NM_001037730
dbSNP: rs758826378
Type: single nucleotide variant
Location: chr20:31259567 (GRCh38)
Gene constraint: LOEUF 1.486 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.46

Full DEFB115 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DEFB115 p.Pro68Leu Uncertain significance ★ ⚠ same residue
DEFB115 p.Ala19Asp Uncertain significance ★ ⚠ same type
DEFB115 p.Asp79Val Uncertain significance ★ ⚠ same type
DEFB115 p.Gln28Arg Uncertain significance ★ ⚠ same type
DEFB115 p.Glu53Asp Uncertain significance ★ ⚠ same type
DEFB115 p.Gly43Asp Uncertain significance ★ ⚠ same type
DEFB115 p.Leu15His Uncertain significance ★ ⚠ same type
DEFB115 p.Leu9Pro 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/defb115-p-pro68ser (accessed [today's date]).

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