Is DNHD1 p.Val300Met (c.898G>A) pathogenic?

DNHD1 p.Val300Met (c.898G>A) is classified Likely benign in DNHD1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-27). AlphaMissense: likely benign (0.2244); Rare (popmax 0.586%, nfe).

How common is DNHD1 p.Val300Met (c.898G>A) in the general population?

DNHD1 p.Val300Met (c.898G>A) is rare (popmax 0.586%, nfe) (gnomAD).

What do computational predictors say about DNHD1 p.Val300Met (c.898G>A)?

AlphaMissense predicts likely benign (score 0.2244) — an in-silico prediction, not a clinical call.

DNHD1 p.Val300Met

c.898G>A · rs150283566 · VCV773243

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2244 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.586%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.2244	likely benign
REVEL	0.076	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 1.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 66 kb · p 5.3e-11 · regional, not allelic
Overall
CADD	25.3	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 0.586% European (non-Finnish) · 6,910/1,179,788 alleles

Filtering AF 0.574% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.569%

Overall 0.482% 7,777/1,613,638 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.586%	171
Remaining individualsnot grpmax-eligible	0.482%	208
Admixed American	0.332%	301
South Asian	0.188%	532
Finnishnot grpmax-eligible	0.133%	753
Ashkenazi Jewishnot grpmax-eligible	0.108%	925
African / African-American	0.0987%	1,014
Middle Eastern	0.0825%	1,212

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.Val300Met
Coding: c.898G>A
MANE Select: NM_144666
dbSNP: rs150283566
Type: single nucleotide variant
Location: chr11:6502904 (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-val300met (accessed [today's date]).

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