Is DNHD1 p.Gln279Pro (c.836A>C) pathogenic?

DNHD1 p.Gln279Pro (c.836A>C) is classified Benign in DNHD1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-01). AlphaMissense: likely benign (0.1037); Common (popmax 18.4%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with DNHD1-related disorder.

What condition is associated with DNHD1 p.Gln279Pro (c.836A>C)?

DNHD1 p.Gln279Pro (c.836A>C) is associated with DNHD1-related disorder (ClinVar).

What do computational predictors say about DNHD1 p.Gln279Pro (c.836A>C)?

AlphaMissense predicts likely benign (score 0.1037) — an in-silico prediction, not a clinical call.

DNHD1 p.Gln279Pro

Q: How common is DNHD1 p.Gln279Pro (c.836A>C) in the general population?

DNHD1 p.Gln279Pro (c.836A>C) is common (popmax 18.4%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.836A>C · rs11605196 · VCV3057035

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1037 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 18.4%, nfe) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

DNHD1-related disorder

Computational evidence

Protein change
AlphaMissense	0.1037	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.54, phastCons 0.54
Regional constraint	o/e 0.90	unconstrained · MANE · 66 kb · p 5.3e-11 · regional, not allelic
Overall
CADD	9.332	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 18.4% European (non-Finnish) · 216,743/1,179,516 alleles

Filtering AF 18.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 18.3%

Overall 16.9% 271,797/1,612,914 alleles · common exomes 251,478/1,460,668 · genomes 20,319/152,246 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	22.5%	4
European (non-Finnish)grpmax	18.4%	5
Middle Eastern	17.8%	6
South Asian	17.8%	6
Remaining individualsnot grpmax-eligible	16.8%	6
Finnishnot grpmax-eligible	12.6%	8
Admixed American	12.3%	8
Amishnot grpmax-eligible	10%	10
African / African-American	5.59%	18
East Asian	2.26%	44

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Gln279Pro
Coding: c.836A>C
MANE Select: NM_144666
dbSNP: rs11605196
Type: single nucleotide variant
Location: chr11:6502842 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 (gnomAD)
Residue 279: 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-gln279pro (accessed [today's date]).

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