Is DNHD1 p.Thr1003= (c.3009T>C) pathogenic?

DNHD1 p.Thr1003= (c.3009T>C) is classified Likely benign in DNHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-19). Very rare (popmax 0.000959%, nfe).

How common is DNHD1 p.Thr1003= (c.3009T>C) in the general population?

DNHD1 p.Thr1003= (c.3009T>C) is very rare (popmax 0.000959%, nfe) (gnomAD).

DNHD1 p.Thr1003=

c.3009T>C · rs942608649 · VCV758621

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000959%, nfe)

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 0.19	GERP -4, phastCons 0.006
Overall
CADD	2.228	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000959% European (non-Finnish) · 11/1,146,990 alleles

Filtering AF 0.000515% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000376%

Overall 0.000967% 15/1,551,532 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00668%	14,971
European (non-Finnish)grpmax	0.000959%	104,272

Finnish 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.Thr1003=
Coding: c.3009T>C
MANE Select: NM_144666
dbSNP: rs942608649
Type: single nucleotide variant
Location: chr11:6538393 (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

DNHD1 p.Arg2928Ter Pathogenic/Likely pathogenic ★★ same type
DNHD1 p.Arg3978Ter Pathogenic/Likely pathogenic ★★ same type
DNHD1 p.Arg4048Ter Pathogenic/Likely pathogenic ★★ same type
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-thr1003 (accessed [today's date]).

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