Is DPEP3 p.Val135Met (c.403G>A) pathogenic?

DPEP3 p.Val135Met (c.403G>A) is classified Uncertain significance in DPEP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-19). AlphaMissense: ambiguous (0.3729); Ultra-rare (popmax 0.012%, afr).

How common is DPEP3 p.Val135Met (c.403G>A) in the general population?

DPEP3 p.Val135Met (c.403G>A) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about DPEP3 p.Val135Met (c.403G>A)?

AlphaMissense predicts ambiguous (score 0.3729) — an in-silico prediction, not a clinical call.

DPEP3 p.Val135Met

c.403G>A · VCV4014519

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3729 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3729	ambiguous
REVEL	0.258	benign-leaning
SaProt	LLR -11.87	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 1.4, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 4,612 bp · p 0.0029 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.012% African / African-American · 9/75,056 alleles

Filtering AF 0.00622% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00467%

Overall 0.00496% 80/1,613,922 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,340
South Asian	0.00769%	13,011
European (non-Finnish)	0.00517%	19,344
Admixed American	0.00333%	30,011
East Asian	0.00223%	44,868

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: DPEP3
Protein: p.Val135Met
Coding: c.403G>A
MANE Select: NM_001370198
Type: single nucleotide variant
Location: chr16:67979650 (GRCh38)
Gene constraint: LOEUF 1.097 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.15 · 2 PDB
Residue 135: a β-strand

Full DPEP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPEP3 c.-44A>T Uncertain significance ★ same type
DPEP3 c.-47C>G Uncertain significance ★ same type
DPEP3 c.-5G>T Uncertain significance ★ same type
DPEP3 c.-62C>T Uncertain significance ★ same type
DPEP3 c.-6C>T Uncertain significance ★ same type
DPEP3 p.Ala11Thr Uncertain significance ★ ⚠ same type
DPEP3 p.Ala157Pro Uncertain significance ★ ⚠ same type
DPEP3 p.Ala284Gly 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/dpep3-p-val135met (accessed [today's date]).

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