Is MTTP p.Asp793Val (c.2378A>T) pathogenic?

MTTP p.Asp793Val (c.2378A>T) is classified Uncertain significance in MTTP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-19). AlphaMissense: ambiguous (0.349); Very rare (popmax 0.0011%, sas).

How common is MTTP p.Asp793Val (c.2378A>T) in the general population?

MTTP p.Asp793Val (c.2378A>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about MTTP p.Asp793Val (c.2378A>T)?

AlphaMissense predicts ambiguous (score 0.349) — an in-silico prediction, not a clinical call.

MTTP p.Asp793Val

c.2378A>T · rs780797954 · VCV2048296

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.349 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.349	ambiguous
REVEL	0.74	pathogenic-leaning
SaProt	LLR -14.71	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 48 kb · p 0.00018 · regional, not allelic
Overall
CADD	23.7	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 0.0011% South Asian · 1/91,074 alleles

Overall 6.2e-05% 1/1,613,842 alleles · very rare exomes 0/1,461,818 · genomes 1/152,024 · joint denominator

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: MTTP
Protein: p.Asp793Val
Coding: c.2378A>T
MANE Select: NM_001386140
dbSNP: rs780797954
Type: single nucleotide variant
Location: chr4:99621096 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.73 · 2 PDB
Residue 793: a β-strand

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

Similar variants

MTTP p.Asp793Ala Uncertain significance ★★ ⚠ same residue
MTTP p.Asp793Gly Uncertain significance ★ ⚠ same residue
MTTP c.1067+1G>C Likely pathogenic ★★ same type
MTTP c.1236+1G>A Pathogenic/Likely pathogenic ★★ same type
MTTP c.1769+2T>C Pathogenic/Likely pathogenic ★★ same type
MTTP c.1867+1G>A Pathogenic ★★ same type
MTTP c.1867+5G>A Pathogenic/Likely pathogenic ★★ same type
MTTP c.1868-2A>G Likely pathogenic ★★ 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/mttp-p-asp793val (accessed [today's date]).

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