Is DNHD1 p.Cys775Arg (c.2323T>C) pathogenic?

DNHD1 p.Cys775Arg (c.2323T>C) is classified Uncertain significance in DNHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-25). AlphaMissense: likely pathogenic (0.6327); Very rare (popmax 0.00595%, sas).

How common is DNHD1 p.Cys775Arg (c.2323T>C) in the general population?

DNHD1 p.Cys775Arg (c.2323T>C) is very rare (popmax 0.00595%, sas) (gnomAD).

What do computational predictors say about DNHD1 p.Cys775Arg (c.2323T>C)?

AlphaMissense predicts likely pathogenic (score 0.6327) — an in-silico prediction, not a clinical call.

DNHD1 p.Cys775Arg

c.2323T>C · VCV4013816

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6327 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00595%, sas)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.6327	likely pathogenic · top 9% in DNHD1
REVEL	0.182	moderately 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 5.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 66 kb · p 5.3e-11 · regional, not allelic
Overall
CADD	21.7	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 0.00595% South Asian · 5/83,988 alleles

Filtering AF 0.00234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00146%

Overall 0.000429% 6/1,397,960 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00595%	16,798
European (non-Finnish)	8.72e-05%	1,146,934

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.Cys775Arg
Coding: c.2323T>C
MANE Select: NM_144666
Type: single nucleotide variant
Location: chr11:6529097 (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

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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-cys775arg (accessed [today's date]).

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