Is DTHD1 p.Ile286Val (c.856A>G) pathogenic?

DTHD1 p.Ile286Val (c.856A>G) is classified Likely benign in DTHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-24). AlphaMissense: likely benign (0.0672); Rare (popmax 0.255%, sas).

How common is DTHD1 p.Ile286Val (c.856A>G) in the general population?

DTHD1 p.Ile286Val (c.856A>G) is rare (popmax 0.255%, sas) (gnomAD).

What do computational predictors say about DTHD1 p.Ile286Val (c.856A>G)?

AlphaMissense predicts likely benign (score 0.0672) — an in-silico prediction, not a clinical call.

DTHD1 p.Ile286Val

c.856A>G · VCV4966818

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0672 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.255%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0672	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -6.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.42	GERP -2
Regional constraint	o/e 0.99	unconstrained · MANE · 62 kb · p 0.66 · regional, not allelic
Overall
CADD	1.93	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM I161V vs ClinVar I286V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.255% South Asian · 207/81,142 alleles

Filtering AF 0.227% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.216%

Overall 0.0144% 220/1,525,096 alleles · rare exomes 211/1,372,860 · genomes 9/152,236 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.255%	392
Remaining individualsnot grpmax-eligible	0.0151%	6,605
European (non-Finnish)	0.00035%	285,695

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.Ile286Val
Coding: c.856A>G
MANE Select: NM_001170700
Type: single nucleotide variant
Location: chr4:36284560 (GRCh38)
Gene constraint: LOEUF 1.034 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.99

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

Similar variants

DTHD1 p.Ile286Thr Uncertain significance ★ ⚠ same residue
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

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-ile286val (accessed [today's date]).

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