Is DLAT p.Val614Phe (c.1840G>T) pathogenic?

DLAT p.Val614Phe (c.1840G>T) is classified Uncertain significance in DLAT (ClinVar, Single submitter, 2 submitters; last evaluated 2024-08-20). AlphaMissense: likely pathogenic (0.8677); Ultra-rare (popmax 0.0561%, afr); Associated with Inborn genetic diseases.

What condition is associated with DLAT p.Val614Phe (c.1840G>T)?

DLAT p.Val614Phe (c.1840G>T) is associated with Inborn genetic diseases (ClinVar).

How common is DLAT p.Val614Phe (c.1840G>T) in the general population?

DLAT p.Val614Phe (c.1840G>T) is ultra-rare (popmax 0.0561%, afr) (gnomAD).

What do computational predictors say about DLAT p.Val614Phe (c.1840G>T)?

AlphaMissense predicts likely pathogenic (score 0.8677) — an in-silico prediction, not a clinical call.

DLAT p.Val614Phe

c.1840G>T · rs201582626 · VCV2342392

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8677 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0561%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8677	likely pathogenic
REVEL	0.578	indeterminate
SaProt	LLR -13.78	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.8	GERP 2.1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 37 kb · p 0.014 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0561% African / African-American · 42/74,860 alleles

Filtering AF 0.0426% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0379%

Overall 0.00285% 46/1,612,500 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0561%	1,782
Admixed American	0.00333%	30,000
Remaining individualsnot grpmax-eligible	0.00321%	31,176

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.Val614Phe
Coding: c.1840G>T
MANE Select: NM_001931
dbSNP: rs201582626
Type: single nucleotide variant
Location: chr11:112062431 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.59 · 13 PDB
Residue 614: a β-strand

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-val614phe (accessed [today's date]).

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