Is MTTP p.Val363Ala (c.1088T>C) pathogenic?

MTTP p.Val363Ala (c.1088T>C) is classified Uncertain significance in MTTP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-29). AlphaMissense: likely benign (0.2582); Very rare (popmax 0.01%, amr); Associated with Inborn genetic diseases.

What condition is associated with MTTP p.Val363Ala (c.1088T>C)?

MTTP p.Val363Ala (c.1088T>C) is associated with Inborn genetic diseases (ClinVar).

How common is MTTP p.Val363Ala (c.1088T>C) in the general population?

MTTP p.Val363Ala (c.1088T>C) is very rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about MTTP p.Val363Ala (c.1088T>C)?

AlphaMissense predicts likely benign (score 0.2582) — an in-silico prediction, not a clinical call.

MTTP p.Val363Ala

c.1088T>C · rs1217629807 · VCV2150276

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2582 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.01%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2582	likely benign
REVEL	0.248	benign-leaning
SaProt	LLR -6.96	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 48 kb · p 0.00018 · regional, not allelic
Overall
CADD	20.4	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 0.01% Admixed American · 6/60,018 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000372% 6/1,613,756 alleles · very rare exomes 6/1,461,482 · genomes 0/152,274 · 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.Val363Ala
Coding: c.1088T>C
MANE Select: NM_001386140
dbSNP: rs1217629807
Type: single nucleotide variant
Location: chr4:99600585 (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 363: the vitellogenin domain; an α-helix

Full MTTP 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

MTTP p.Ala144Asp Uncertain significance ★★ ⚠ same condition
MTTP p.Ala339Val Uncertain significance ★★ ⚠ same condition
MTTP p.Ala464Thr Uncertain significance ★★ ⚠ same condition
MTTP p.Ala493Ser Uncertain significance ★★ ⚠ same condition
MTTP p.Ala577Thr Uncertain significance ★★ ⚠ same condition
MTTP p.Ala883Asp Uncertain significance ★★ ⚠ same condition
MTTP p.Arg312Gly Uncertain significance ★★ ⚠ same condition
MTTP p.Arg58His 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/mttp-p-val363ala (accessed [today's date]).

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