Is DPEP3 p.Ser271Trp (c.812C>G) pathogenic?

DPEP3 p.Ser271Trp (c.812C>G) is classified Uncertain significance in DPEP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-20). AlphaMissense: likely pathogenic (0.5708); Ultra-rare (popmax 0.0493%, mid).

How common is DPEP3 p.Ser271Trp (c.812C>G) in the general population?

DPEP3 p.Ser271Trp (c.812C>G) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

What do computational predictors say about DPEP3 p.Ser271Trp (c.812C>G)?

AlphaMissense predicts likely pathogenic (score 0.5708) — an in-silico prediction, not a clinical call.

DPEP3 p.Ser271Trp

c.812C>G · VCV4014520

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5708 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5708	likely pathogenic
REVEL	0.524	indeterminate
SaProt	LLR -13.22	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.84 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 4,612 bp · p 0.0029 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0493% Middle Eastern · 3/6,084 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00715%

Overall 0.0031% 50/1,613,720 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,028
Remaining individualsnot grpmax-eligible	0.00961%	10,410
African / African-American	0.00534%	18,726
European (non-Finnish)	0.00297%	33,710
Admixed American	0.00167%	59,968
South Asian	0.0011%	91,066

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.Ser271Trp
Coding: c.812C>G
MANE Select: NM_001370198
Type: single nucleotide variant
Location: chr16:67977774 (GRCh38)
Gene constraint: LOEUF 1.097 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.15 · 2 PDB

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-ser271trp (accessed [today's date]).

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