Is DNPH1 p.Pro7Ala (c.19C>G) pathogenic?

DNPH1 p.Pro7Ala (c.19C>G) is classified Uncertain significance in DNPH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-15). AlphaMissense: likely benign (0.0511); Ultra-rare (popmax 0.0105%, afr).

How common is DNPH1 p.Pro7Ala (c.19C>G) in the general population?

DNPH1 p.Pro7Ala (c.19C>G) is ultra-rare (popmax 0.0105%, afr) (gnomAD).

What do computational predictors say about DNPH1 p.Pro7Ala (c.19C>G)?

AlphaMissense predicts likely benign (score 0.0511) — an in-silico prediction, not a clinical call.

DNPH1 p.Pro7Ala

c.19C>G · VCV3273259

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0511 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0105%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0511	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -6.12	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 -0.15	GERP -3.5
Regional constraint	o/e 1.03	unconstrained · MANE · 3,720 bp · p 0.67 · regional, not allelic
Overall
CADD	6.296	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 0.0105% African / African-American · 7/66,352 alleles

Filtering AF 0.00487% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00351%

Overall 0.000514% 7/1,362,652 alleles · ultra-rare exomes 0/1,210,520 · genomes 7/152,132 · joint denominator

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.Pro7Ala
Coding: c.19C>G
MANE Select: NM_006443
Type: single nucleotide variant
Location: chr6:43229438 (GRCh38)
Gene constraint: LOEUF 1.914 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.50 · 25 PDB

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-pro7ala (accessed [today's date]).

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