Is DNHD1 p.Phe295Val (c.883T>G) pathogenic?

DNHD1 p.Phe295Val (c.883T>G) is classified Uncertain significance in DNHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). AlphaMissense: likely pathogenic (0.6068); Very rare (popmax 0.000424%, nfe).

How common is DNHD1 p.Phe295Val (c.883T>G) in the general population?

DNHD1 p.Phe295Val (c.883T>G) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about DNHD1 p.Phe295Val (c.883T>G)?

AlphaMissense predicts likely pathogenic (score 0.6068) — an in-silico prediction, not a clinical call.

DNHD1 p.Phe295Val

c.883T>G · rs928725864 · VCV2589605

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6068 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.6068	likely pathogenic · top 10% in DNHD1
REVEL	0.288	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 66 kb · p 5.3e-11 · regional, not allelic
Overall
CADD	24.6	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 0.000424% European (non-Finnish) · 5/1,179,850 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,461,480 alleles · very rare

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: DNHD1
Protein: p.Phe295Val
Coding: c.883T>G
MANE Select: NM_144666
dbSNP: rs928725864
Type: single nucleotide variant
Location: chr11:6502889 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 (gnomAD)

Full DNHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNHD1 p.Arg2928Ter Pathogenic/Likely pathogenic ★★ same type
DNHD1 p.Arg3978Ter Pathogenic/Likely pathogenic ★★ same type
DNHD1 p.Arg4048Ter Pathogenic/Likely pathogenic ★★ same type
DNHD1 p.Glu1153Ter Pathogenic/Likely pathogenic ★★ same type
DNHD1 p.Tyr2166Ter Pathogenic/Likely pathogenic ★★ same type
DNHD1 p.Arg1582Trp Uncertain significance ★★ same type
DNHD1 p.Arg1873Ser Uncertain significance ★★ same type
DNHD1 p.Arg2555Trp 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/dnhd1-p-phe295val (accessed [today's date]).

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