Is DNPH1 p.Ala87Val (c.260C>T) pathogenic?

DNPH1 p.Ala87Val (c.260C>T) is classified Uncertain significance in DNPH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-15). AlphaMissense: ambiguous (0.4994); Very rare (popmax 0.00439%, sas).

How common is DNPH1 p.Ala87Val (c.260C>T) in the general population?

DNPH1 p.Ala87Val (c.260C>T) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about DNPH1 p.Ala87Val (c.260C>T)?

AlphaMissense predicts ambiguous (score 0.4994) — an in-silico prediction, not a clinical call.

DNPH1 p.Ala87Val

c.260C>T · rs781456801 · VCV2485439

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4994 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Computational evidence

Protein change
AlphaMissense	0.4994	ambiguous
REVEL	0.345	indeterminate
SaProt	LLR -12.79	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 3,720 bp · p 0.67 · regional, not allelic
Overall
CADD	24.9	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 0.00439% South Asian · 4/91,014 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00225%

Overall 0.00292% 47/1,612,112 alleles · very rare exomes 44/1,460,010 · genomes 3/152,102 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,815
South Asiangrpmax	0.00439%	22,753
European (non-Finnish)	0.00339%	29,495

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala87Val
Coding: c.260C>T
MANE Select: NM_006443
dbSNP: rs781456801
Type: single nucleotide variant
Location: chr6:43226332 (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.Arg125His Uncertain significance ★ ⚠ same type
DNPH1 p.Arg132Gly Uncertain significance ★ same type
DNPH1 p.Arg132Trp Uncertain significance ★ ⚠ same type
DNPH1 p.Arg139Gln 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-ala87val (accessed [today's date]).

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