Is DLAT p.Pro333Arg (c.998C>G) pathogenic?

DLAT p.Pro333Arg (c.998C>G) is classified Uncertain significance in DLAT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-20). AlphaMissense: likely benign (0.102); Ultra-rare (popmax 0.0223%, eas).

How common is DLAT p.Pro333Arg (c.998C>G) in the general population?

DLAT p.Pro333Arg (c.998C>G) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

What do computational predictors say about DLAT p.Pro333Arg (c.998C>G)?

AlphaMissense predicts likely benign (score 0.102) — an in-silico prediction, not a clinical call.

DLAT p.Pro333Arg

c.998C>G · rs782453793 · VCV1695817

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.102 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.102	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -11.34	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.7, phastCons 0.82
Regional constraint	o/e 0.91	unconstrained · MANE · 37 kb · p 0.014 · regional, not allelic
Overall
CADD	22.6	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 0.0223% East Asian · 10/44,882 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00916%

Overall 0.000682% 11/1,613,766 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,488
South Asian	0.0011%	91,050

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.Pro333Arg
Coding: c.998C>G
MANE Select: NM_001931
dbSNP: rs782453793
Type: single nucleotide variant
Location: chr11:112039266 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.59 · 13 PDB
Residue 333: the 'disordered' region

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

Similar variants

DLAT c.976-1G>A Pathogenic/Likely pathogenic ★★ same type
DLAT p.Arg435Ter Pathogenic ★★ same type
DLAT p.Glu138Ter Pathogenic ★★ same type
DLAT p.Val157Gly Likely pathogenic ★★ same type
DLAT c.1130-6T>G Uncertain significance ★★ same type
DLAT p.Ala109Thr Uncertain significance ★★ ⚠ same type
DLAT p.Ala191Gly Uncertain significance ★★ ⚠ same type
DLAT p.Ala191Val 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/dlat-p-pro333arg (accessed [today's date]).

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