Is DLAT p.Val404Ala (c.1211T>C) pathogenic?

DLAT p.Val404Ala (c.1211T>C) is classified Likely benign in DLAT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-07). AlphaMissense: likely benign (0.0549); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with DLAT p.Val404Ala (c.1211T>C)?

DLAT p.Val404Ala (c.1211T>C) is associated with Inborn genetic diseases (ClinVar).

How common is DLAT p.Val404Ala (c.1211T>C) in the general population?

DLAT p.Val404Ala (c.1211T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DLAT p.Val404Ala (c.1211T>C)?

AlphaMissense predicts likely benign (score 0.0549) — an in-silico prediction, not a clinical call.

DLAT p.Val404Ala

c.1211T>C · VCV3502228

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0549 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0549	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -5.37	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 2.2	GERP -2, phastCons 0.87
Regional constraint	o/e 0.91	unconstrained · MANE · 37 kb · p 0.014 · regional, not allelic
Overall
CADD	12.96	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 0.00167% Admixed American · 1/60,000 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.00062% 10/1,613,966 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,000
Remaining individualsnot grpmax-eligible	0.0016%	62,484
South Asian	0.0011%	91,084
European (non-Finnish)	0.000593%	168,572

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: DLAT
Protein: p.Val404Ala
Coding: c.1211T>C
MANE Select: NM_001931
Type: single nucleotide variant
Location: chr11:112045151 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.59 · 13 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DLAT p.Val157Gly Likely pathogenic ★★ same condition
DLAT p.Ala253Ser Uncertain significance ★★ ⚠ same condition
DLAT p.Arg429Ser Uncertain significance ★★ ⚠ same condition
DLAT p.Arg430Gln Uncertain significance ★★ ⚠ same condition
DLAT p.Arg56Pro Uncertain significance ★★ ⚠ same condition
DLAT p.Arg70Trp Uncertain significance ★★ ⚠ same condition
DLAT p.Asp390Asn Uncertain significance ★★ ⚠ same condition
DLAT p.Glu469Gly Uncertain significance ★★ ⚠ same condition

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/dlat-p-val404ala (accessed [today's date]).

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