Is DNPEP p.Phe472Ser (c.1415T>C) pathogenic?

DNPEP p.Phe472Ser (c.1415T>C) is classified Uncertain significance in DNPEP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-05). AlphaMissense: likely pathogenic (0.916); Very rare (popmax 0.00267%, afr).

How common is DNPEP p.Phe472Ser (c.1415T>C) in the general population?

DNPEP p.Phe472Ser (c.1415T>C) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about DNPEP p.Phe472Ser (c.1415T>C)?

AlphaMissense predicts likely pathogenic (score 0.916) — an in-silico prediction, not a clinical call.

DNPEP p.Phe472Ser

c.1415T>C · VCV3273254

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.916 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.916	likely pathogenic
REVEL	0.789	moderately pathogenic-leaning
SaProt	LLR -11.88	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.2 · regional, not allelic
Overall
CADD	28.0	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 0.00267% African / African-American · 2/74,928 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00167% 27/1,613,968 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,464
European (non-Finnish)	0.00212%	47,198

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: DNPEP
Protein: p.Phe472Ser
Coding: c.1415T>C
MANE Select: NM_012100
Type: single nucleotide variant
Location: chr2:219374335 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.95 · 1 PDB
Residue 472: an α-helix

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

Similar variants

DNPEP p.Tyr308Cys Uncertain significance ★★ ⚠ same type
DNPEP p.Ile171Val Benign ★★ same type
DNPEP p.Ala204Thr Uncertain significance ★ ⚠ same type
DNPEP p.Ala221Thr Uncertain significance ★ ⚠ same type
DNPEP p.Ala263Ser Uncertain significance ★ ⚠ same type
DNPEP p.Ala27Val Uncertain significance ★ ⚠ same type
DNPEP p.Ala321Ser Uncertain significance ★ ⚠ same type
DNPEP p.Arg114His 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/dnpep-p-phe472ser (accessed [today's date]).

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