Is DNHD1 p.Cys1682Arg (c.5044T>C) pathogenic?

DNHD1 p.Cys1682Arg (c.5044T>C) is classified Uncertain significance in DNHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-18). AlphaMissense: likely pathogenic (0.7072); Ultra-rare (popmax 0.0438%, afr).

How common is DNHD1 p.Cys1682Arg (c.5044T>C) in the general population?

DNHD1 p.Cys1682Arg (c.5044T>C) is ultra-rare (popmax 0.0438%, afr) (gnomAD).

What do computational predictors say about DNHD1 p.Cys1682Arg (c.5044T>C)?

AlphaMissense predicts likely pathogenic (score 0.7072) — an in-silico prediction, not a clinical call.

DNHD1 p.Cys1682Arg

c.5044T>C · VCV3841655

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7072 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0438%, afr)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.7072	likely pathogenic · top 7% in DNHD1
REVEL	0.183	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 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 66 kb · p 5.3e-11 · regional, not allelic
Overall
CADD	25.1	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 0.0438% African / African-American · 32/73,056 alleles

Filtering AF 0.0318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0278%

Overall 0.00219% 34/1,551,660 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0438%	2,283
Admixed American	0.00392%	25,499

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.Cys1682Arg
Coding: c.5044T>C
MANE Select: NM_144666
Type: single nucleotide variant
Location: chr11:6545983 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 (gnomAD)
Residue 1682: a UniProt-annotated variant site (in spgf65)

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

Similar variants

DNHD1 p.Cys1682Ser Uncertain significance ★ ⚠ same residue
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

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-cys1682arg (accessed [today's date]).

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