Is DUT p.Ala235Ser (c.703G>T) pathogenic?

DUT p.Ala235Ser (c.703G>T) is classified Uncertain significance in DUT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: likely benign (0.0752); Very rare (popmax 0.00388%, amr).

How common is DUT p.Ala235Ser (c.703G>T) in the general population?

DUT p.Ala235Ser (c.703G>T) is very rare (popmax 0.00388%, amr) (gnomAD).

What do computational predictors say about DUT p.Ala235Ser (c.703G>T)?

AlphaMissense predicts likely benign (score 0.0752) — an in-silico prediction, not a clinical call.

DUT p.Ala235Ser

c.703G>T · VCV4245633

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0752 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00388%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0752	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -6.06	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.20	acceptor loss, 23 bp away · masked 0 · deltas
Pangolin	Δ0.54	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.8	GERP 4.2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 11 kb · p 0.68 · regional, not allelic
Overall
CADD	18.27	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00388% Admixed American · 2/51,604 alleles

Filtering AF 0.000643% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00024%

Overall 0.000141% 2/1,422,492 alleles · very rare

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: DUT
Protein: p.Ala235Ser
Coding: c.703G>T
MANE Select: NM_001025248
Type: single nucleotide variant
Location: chr15:48342022 (GRCh38)
Gene constraint: LOEUF 1.684 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.51 · 12 PDB

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

Similar variants

DUT p.Tyr142Cys Likely pathogenic ★ ⚠ same type
DUT p.Arg173Trp Uncertain significance ★ ⚠ same type
DUT p.Arg216Gln Uncertain significance ★ ⚠ same type
DUT p.Asp192His Uncertain significance ★ ⚠ same type
DUT p.Gln219His Uncertain significance ★ ⚠ same type
DUT p.Glu223Lys Uncertain significance ★ ⚠ same type
DUT p.Glu240Lys Uncertain significance ★ ⚠ same type
DUT p.Gly135Ala 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/dut-p-ala235ser (accessed [today's date]).

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