Is DTHD1 p.Val201= (c.603A>C) pathogenic?

DTHD1 p.Val201= (c.603A>C) is classified Benign in DTHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-26). Common (popmax 25.5%, nfe) — too common for a highly-penetrant pathogenic allele.

DTHD1 p.Val201=

Q: How common is DTHD1 p.Val201= (c.603A>C) in the general population?

DTHD1 p.Val201= (c.603A>C) is common (popmax 25.5%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.603A>C · VCV4966809

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 25.5%, nfe) — too common for a highly-penetrant pathogenic allele

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	GERP -0.55, phastCons 0.88
Overall
CADD	1.061	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 25.5% European (non-Finnish) · 292,990/1,146,802 alleles

Filtering AF 25.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 25.4%

Overall 24.3% 373,789/1,537,068 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	38.7%	3
Ashkenazi Jewishnot grpmax-eligible	34.1%	3
European (non-Finnish)grpmax	25.5%	4
South Asian	25.5%	4
Remaining individualsnot grpmax-eligible	24.3%	4
Middle Eastern	23.7%	4
Admixed American	21.4%	5
Finnishnot grpmax-eligible	16.8%	6
African / African-American	16%	6
East Asian	7%	14

Amish 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: DTHD1
Protein: p.Val201=
Coding: c.603A>C
MANE Select: NM_001170700
Type: single nucleotide variant
Location: chr4:36284307 (GRCh38)
Gene constraint: LOEUF 1.034 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.99
Residue 201: the zu5 1 domain

Full DTHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DTHD1 c.1218+1G>A Uncertain significance ★★ same type
DTHD1 c.1219-2A>G Uncertain significance ★★ same type
DTHD1 p.Ala552Ser Uncertain significance ★★ ⚠ same type
DTHD1 p.Ala811Asp Uncertain significance ★★ ⚠ same type
DTHD1 p.Arg326Gln Uncertain significance ★★ ⚠ same type
DTHD1 p.Arg371Cys Uncertain significance ★★ ⚠ same type
DTHD1 p.Arg447Gln Uncertain significance ★★ ⚠ same type
DTHD1 p.Arg447Ter 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/dthd1-p-val201 (accessed [today's date]).

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