Is DNPH1 p.Arg156Pro (c.467G>C) pathogenic?

DNPH1 p.Arg156Pro (c.467G>C) is classified Uncertain significance in DNPH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: ambiguous (0.4108); Ultra-rare (popmax 0.0108%, nfe).

How common is DNPH1 p.Arg156Pro (c.467G>C) in the general population?

DNPH1 p.Arg156Pro (c.467G>C) is ultra-rare (popmax 0.0108%, nfe) (gnomAD).

What do computational predictors say about DNPH1 p.Arg156Pro (c.467G>C)?

AlphaMissense predicts ambiguous (score 0.4108) — an in-silico prediction, not a clinical call.

DNPH1 p.Arg156Pro

c.467G>C · rs373245097 · VCV2511722

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4108 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0108%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4108	ambiguous
REVEL	0.158	moderately benign-leaning
SaProt	LLR -15.76	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 -2.9	GERP -3.5
Regional constraint	o/e 1.03	unconstrained · MANE · 3,720 bp · p 0.67 · regional, not allelic
Overall
CADD	19.66	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 0.0108% European (non-Finnish) · 127/1,180,054 alleles

Filtering AF 0.00919% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00863%

Overall 0.00805% 130/1,614,084 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0108%	9,292
African / African-American	0.004%	24,974

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: DNPH1
Protein: p.Arg156Pro
Coding: c.467G>C
MANE Select: NM_006443
dbSNP: rs373245097
Type: single nucleotide variant
Location: chr6:43225791 (GRCh38)
Gene constraint: LOEUF 1.914 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.50 · 25 PDB
Residue 156: an α-helix

Full DNPH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNPH1 p.Ala134Thr Uncertain significance ★ ⚠ same type
DNPH1 p.Ala22Thr Uncertain significance ★ ⚠ same type
DNPH1 p.Ala58Glu Uncertain significance ★ ⚠ same type
DNPH1 p.Ala69Pro Uncertain significance ★ ⚠ same type
DNPH1 p.Ala87Val Uncertain significance ★ same type
DNPH1 p.Arg125His Uncertain significance ★ ⚠ same type
DNPH1 p.Arg132Gly Uncertain significance ★ same type
DNPH1 p.Arg132Trp 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/dnph1-p-arg156pro (accessed [today's date]).

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