Is DNHD1 p.Phe363= (c.1089C>T) pathogenic?

DNHD1 p.Phe363= (c.1089C>T) is classified Benign in DNHD1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-04-13). Common (popmax 36.4%, amr) — too common for a highly-penetrant pathogenic allele; Associated with DNHD1-related disorder.

What condition is associated with DNHD1 p.Phe363= (c.1089C>T)?

DNHD1 p.Phe363= (c.1089C>T) is associated with DNHD1-related disorder (ClinVar).

DNHD1 p.Phe363=

Q: How common is DNHD1 p.Phe363= (c.1089C>T) in the general population?

DNHD1 p.Phe363= (c.1089C>T) is common (popmax 36.4%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1089C>T · rs10839568 · VCV3060931

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 36.4%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

DNHD1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.52, phastCons 1
Overall
CADD	11.97	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 36.4% Admixed American · 21,832/60,006 alleles

Filtering AF 36% ClinGen BA1/BS1 input FAF95, joint · FAF99 35.8%

Overall 30.7% 495,892/1,613,990 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	36.4%	3
Amishnot grpmax-eligible	34.8%	3
European (non-Finnish)	33.1%	3
Finnishnot grpmax-eligible	29.3%	3
Remaining individualsnot grpmax-eligible	28.1%	4
Middle Eastern	26.2%	4
Ashkenazi Jewishnot grpmax-eligible	24.2%	4
South Asian	22.1%	5
African / African-American	16.5%	6
East Asian	13%	8

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.Phe363=
Coding: c.1089C>T
MANE Select: NM_144666
dbSNP: rs10839568
Type: single nucleotide variant
Location: chr11:6509048 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 (gnomAD)

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-phe363 (accessed [today's date]).

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