Is DPEP1 p.Ser281Phe (c.842C>T) pathogenic?

DPEP1 p.Ser281Phe (c.842C>T) is classified Uncertain significance in DPEP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-22). AlphaMissense: likely benign (0.2756); Ultra-rare (popmax 0.0333%, afr).

How common is DPEP1 p.Ser281Phe (c.842C>T) in the general population?

DPEP1 p.Ser281Phe (c.842C>T) is ultra-rare (popmax 0.0333%, afr) (gnomAD).

What do computational predictors say about DPEP1 p.Ser281Phe (c.842C>T)?

AlphaMissense predicts likely benign (score 0.2756) — an in-silico prediction, not a clinical call.

DPEP1 p.Ser281Phe

c.842C>T · VCV3273565

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2756 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0333%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2756	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -9.54	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 1.3	GERP -2.9, phastCons 0.21
Regional constraint	o/e 1.20	unconstrained · MANE · 7,808 bp · p 2.9e-06 · regional, not allelic
Overall
CADD	21.1	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 0.0333% African / African-American · 25/75,056 alleles

Filtering AF 0.0231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00198% 32/1,612,856 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0333%	3,002
South Asian	0.00549%	18,217
Admixed American	0.00333%	30,013

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: DPEP1
Protein: p.Ser281Phe
Coding: c.842C>T
MANE Select: NM_001389466
Type: single nucleotide variant
Location: chr16:89637541 (GRCh38)
Gene constraint: LOEUF 1.505 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.34 · 2 PDB
Residue 281: an α-helix

Full DPEP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPEP1 p.Ala155Glu Uncertain significance ★ ⚠ same type
DPEP1 p.Ala155Thr Uncertain significance ★ ⚠ same type
DPEP1 p.Ala296Val Uncertain significance ★ ⚠ same type
DPEP1 p.Ala326Thr Uncertain significance ★ ⚠ same type
DPEP1 p.Ala402Asp Uncertain significance ★ ⚠ same type
DPEP1 p.Arg107Leu Uncertain significance ★ ⚠ same type
DPEP1 p.Arg110Trp Uncertain significance ★ ⚠ same type
DPEP1 p.Arg126Gln 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/dpep1-p-ser281phe (accessed [today's date]).

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