Is DNHD1 p.Leu190= (c.570G>T) pathogenic?

DNHD1 p.Leu190= (c.570G>T) is classified Benign in DNHD1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-10-28). Common (popmax 51.7%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with DNHD1-related disorder.

What condition is associated with DNHD1 p.Leu190= (c.570G>T)?

DNHD1 p.Leu190= (c.570G>T) is associated with DNHD1-related disorder (ClinVar).

DNHD1 p.Leu190=

Q: How common is DNHD1 p.Leu190= (c.570G>T) in the general population?

DNHD1 p.Leu190= (c.570G>T) is common (popmax 51.7%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.570G>T · rs11040899 · VCV3060797

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 51.7%, nfe) — 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 0.077	GERP -3.1, phastCons 0.61
Overall
CADD	0.581	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 51.7% European (non-Finnish) · 609,856/1,179,958 alleles

Filtering AF 51.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 51.5%

Overall 48.8% 787,284/1,613,972 alleles · common

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	51.7%	2
Admixed American	50%	2
Ashkenazi Jewishnot grpmax-eligible	47.7%	2
Remaining individualsnot grpmax-eligible	46.7%	2
Middle Eastern	46.1%	2
Amishnot grpmax-eligible	44.9%	2
South Asian	44.5%	2
Finnishnot grpmax-eligible	41.9%	2
African / African-American	34.7%	3
East Asian	16.9%	6

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.Leu190=
Coding: c.570G>T
MANE Select: NM_144666
dbSNP: rs11040899
Type: single nucleotide variant
Location: chr11:6498785 (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-leu190 (accessed [today's date]).

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