Is DNHD1 p.Val240Glu (c.719T>A) pathogenic?

DNHD1 p.Val240Glu (c.719T>A) is classified Benign in DNHD1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-10-28). AlphaMissense: likely benign (0.0508); Common (popmax 65.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with DNHD1-related disorder.

What condition is associated with DNHD1 p.Val240Glu (c.719T>A)?

DNHD1 p.Val240Glu (c.719T>A) is associated with DNHD1-related disorder (ClinVar).

What do computational predictors say about DNHD1 p.Val240Glu (c.719T>A)?

AlphaMissense predicts likely benign (score 0.0508) — an in-silico prediction, not a clinical call.

DNHD1 p.Val240Glu

Q: How common is DNHD1 p.Val240Glu (c.719T>A) in the general population?

DNHD1 p.Val240Glu (c.719T>A) is common (popmax 65.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.719T>A · rs2555158 · VCV3059265

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0508 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 65.8%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

DNHD1-related disorder

Computational evidence

Protein change
AlphaMissense	0.0508	likely benign
REVEL	0.017	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 2.3	GERP -3.5, phastCons 0.005
Regional constraint	o/e 0.90	unconstrained · MANE · 66 kb · p 5.3e-11 · regional, not allelic
Overall
CADD	1.713	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 65.8% African / African-American · 49,196/74,784 alleles

Filtering AF 65.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 65.1%

Overall 52.2% 839,282/1,608,342 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	65.8%	2
European (non-Finnish)	53.5%	2
Admixed American	53.3%	2
Amishnot grpmax-eligible	51.7%	2
Ashkenazi Jewishnot grpmax-eligible	51.5%	2
Middle Eastern	51.1%	2
Remaining individualsnot grpmax-eligible	50.8%	2
South Asian	46.3%	2
Finnishnot grpmax-eligible	44.7%	2
East Asian	17.3%	6

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.Val240Glu
Coding: c.719T>A
MANE Select: NM_144666
dbSNP: rs2555158
Type: single nucleotide variant
Location: chr11:6498934 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 (gnomAD)
Residue 240: a UniProt-annotated variant site (in)

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

Disease context

DNHD1-related disorder

Similar variants

DNHD1 p.Glu4486Lys Uncertain significance ★★ ⚠ same condition
DNHD1 p.His4162Leu Uncertain significance ★★ ⚠ same condition
DNHD1 p.Arg2840Gln Uncertain significance ★ ⚠ same condition
DNHD1 p.Gln895Ter Conflicting classifications of pathogenicity ★ same condition
DNHD1 p.His3335Arg Uncertain significance ★ ⚠ same condition
DNHD1 p.Ala657Ser Uncertain significance ⚠ same condition
DNHD1 p.Glu971Lys Uncertain significance ⚠ same condition
DNHD1 p.Met1535Val Uncertain significance ⚠ same condition

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-val240glu (accessed [today's date]).

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