Is DTWD1 p.Leu36Pro (c.107T>C) pathogenic?

DTWD1 p.Leu36Pro (c.107T>C) is classified Uncertain significance in DTWD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-24). AlphaMissense: likely pathogenic (0.8782); Very rare (popmax 0.00533%, afr).

How common is DTWD1 p.Leu36Pro (c.107T>C) in the general population?

DTWD1 p.Leu36Pro (c.107T>C) is very rare (popmax 0.00533%, afr) (gnomAD).

What do computational predictors say about DTWD1 p.Leu36Pro (c.107T>C)?

AlphaMissense predicts likely pathogenic (score 0.8782) — an in-silico prediction, not a clinical call.

DTWD1 p.Leu36Pro

c.107T>C · VCV4662346

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8782 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00533%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8782	likely pathogenic
REVEL	0.26	benign-leaning
SaProt	LLR -14.37	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 3.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 18 kb · p 0.72 · regional, not allelic
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00533% African / African-American · 4/75,028 alleles

Filtering AF 0.00174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000411% 6/1,461,342 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00533%	18,757
Remaining individualsnot grpmax-eligible	0.0032%	31,236

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: DTWD1
Protein: p.Leu36Pro
Coding: c.107T>C
MANE Select: NM_001144955
Type: single nucleotide variant
Location: chr15:49625274 (GRCh38)
Gene constraint: LOEUF 1.283 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.50

Full DTWD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DTWD1 p.Ala31Ser Uncertain significance ★ ⚠ same type
DTWD1 p.Arg178Cys Uncertain significance ★ ⚠ same type
DTWD1 p.Arg178His Uncertain significance ★ ⚠ same type
DTWD1 p.Arg238His Uncertain significance ★ ⚠ same type
DTWD1 p.Asn210Ser Uncertain significance ★ ⚠ same type
DTWD1 p.Asn78His Uncertain significance ★ ⚠ same type
DTWD1 p.Asp188Val Uncertain significance ★ ⚠ same type
DTWD1 p.Asp275Asn 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/dtwd1-p-leu36pro (accessed [today's date]).

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