Is DNHD1 p.Arg1192His (c.3575G>A) pathogenic?

DNHD1 p.Arg1192His (c.3575G>A) is classified Uncertain significance in DNHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-15). AlphaMissense: likely benign (0.0616); Ultra-rare (popmax 0.0922%, nfe).

How common is DNHD1 p.Arg1192His (c.3575G>A) in the general population?

DNHD1 p.Arg1192His (c.3575G>A) is ultra-rare (popmax 0.0922%, nfe) (gnomAD).

What do computational predictors say about DNHD1 p.Arg1192His (c.3575G>A)?

AlphaMissense predicts likely benign (score 0.0616) — an in-silico prediction, not a clinical call.

DNHD1 p.Arg1192His

c.3575G>A · rs200288379 · VCV3084708

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0616 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0922%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0616	likely benign
REVEL	0.005	strongly 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 -1.8	GERP -3.5
Regional constraint	o/e 0.90	unconstrained · MANE · 66 kb · p 5.3e-11 · regional, not allelic
Overall
CADD	1.42	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 0.0922% European (non-Finnish) · 1,058/1,146,940 alleles

Filtering AF 0.0876% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0858%

Overall 0.0723% 1,121/1,551,528 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0922%	1,084
Remaining individualsnot grpmax-eligible	0.0732%	1,366
African / African-American	0.0192%	5,218
Admixed American	0.00785%	12,745
Finnishnot grpmax-eligible	0.00167%	59,894

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.Arg1192His
Coding: c.3575G>A
MANE Select: NM_144666
dbSNP: rs200288379
Type: single nucleotide variant
Location: chr11:6540030 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 (gnomAD)

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-arg1192his (accessed [today's date]).

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