Is DNHD1 p.Ala1994Val (c.5981C>T) pathogenic?

DNHD1 p.Ala1994Val (c.5981C>T) is classified Uncertain significance in DNHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-10). AlphaMissense: likely benign (0.2212); Ultra-rare (popmax 0.0166%, mid).

How common is DNHD1 p.Ala1994Val (c.5981C>T) in the general population?

DNHD1 p.Ala1994Val (c.5981C>T) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about DNHD1 p.Ala1994Val (c.5981C>T)?

AlphaMissense predicts likely benign (score 0.2212) — an in-silico prediction, not a clinical call.

DNHD1 p.Ala1994Val

c.5981C>T · rs777555724 · VCV2387928

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2212 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.2212	likely benign
REVEL	0.126	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 7.7	GERP 1.4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 66 kb · p 5.3e-11 · regional, not allelic
Overall
CADD	26.1	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 0.0166% Middle Eastern · 1/6,014 alleles

Filtering AF 0.0091% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00722%

Overall 0.00664% 103/1,551,378 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,014
South Asian	0.0155%	6,466
African / African-American	0.00958%	10,434
Admixed American	0.00785%	12,742
European (non-Finnish)	0.00637%	15,711
Remaining individualsnot grpmax-eligible	0.00499%	20,028
East Asian	0.00489%	20,451

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.Ala1994Val
Coding: c.5981C>T
MANE Select: NM_144666
dbSNP: rs777555724
Type: single nucleotide variant
Location: chr11:6546920 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 (gnomAD)
Residue 1994: a UniProt-annotated variant site (in spgf65)

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

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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-ala1994val (accessed [today's date]).

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