Is MTTP p.Val862Ile (c.2584G>A) pathogenic?

MTTP p.Val862Ile (c.2584G>A) is classified Uncertain significance in MTTP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-02-21). AlphaMissense: likely benign (0.0656); Very rare (popmax 0.00891%, eas); Associated with Inborn genetic diseases.

What condition is associated with MTTP p.Val862Ile (c.2584G>A)?

MTTP p.Val862Ile (c.2584G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MTTP p.Val862Ile (c.2584G>A) in the general population?

MTTP p.Val862Ile (c.2584G>A) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about MTTP p.Val862Ile (c.2584G>A)?

AlphaMissense predicts likely benign (score 0.0656) — an in-silico prediction, not a clinical call.

MTTP p.Val862Ile

c.2584G>A · rs760443132 · VCV2177381

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0656 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0656	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -6.97	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 0.83	GERP -2.1, phastCons 0.001
Regional constraint	o/e 0.89	unconstrained · MANE · 48 kb · p 0.00018 · regional, not allelic
Overall
CADD	3.254	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 0.00891% East Asian · 4/44,880 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00198% 32/1,613,938 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,220
South Asian	0.00329%	30,364
Remaining individualsnot grpmax-eligible	0.0032%	31,242
European (non-Finnish)	0.00186%	53,634
African / African-American	0.00133%	74,920

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.Val862Ile
Coding: c.2584G>A
MANE Select: NM_001386140
dbSNP: rs760443132
Type: single nucleotide variant
Location: chr4:99622747 (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 862: a β-strand

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.Val862= Likely benign ★ same residue
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

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-val862ile (accessed [today's date]).

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