Is MTTP p.Thr285Arg (c.854C>G) pathogenic?

MTTP p.Thr285Arg (c.854C>G) is classified Uncertain significance in MTTP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-11-30). AlphaMissense: likely benign (0.0648); Very rare (popmax 0.00763%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MTTP p.Thr285Arg (c.854C>G)?

MTTP p.Thr285Arg (c.854C>G) is associated with Inborn genetic diseases (ClinVar).

How common is MTTP p.Thr285Arg (c.854C>G) in the general population?

MTTP p.Thr285Arg (c.854C>G) is very rare (popmax 0.00763%, nfe) (gnomAD).

What do computational predictors say about MTTP p.Thr285Arg (c.854C>G)?

AlphaMissense predicts likely benign (score 0.0648) — an in-silico prediction, not a clinical call.

MTTP p.Thr285Arg

c.854C>G · rs566965111 · VCV2202559

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0648 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00763%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0648	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -5.61	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 -0.77	GERP -3.5
Regional constraint	o/e 0.89	unconstrained · MANE · 48 kb · p 0.00018 · regional, not allelic
Overall
CADD	7.192	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 0.00763% European (non-Finnish) · 90/1,179,922 alleles

Filtering AF 0.00631% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00584%

Overall 0.00595% 96/1,613,866 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00763%	13,110
Remaining individualsnot grpmax-eligible	0.0048%	20,827
Admixed American	0.00333%	29,990
African / African-American	0.00134%	74,892

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.Thr285Arg
Coding: c.854C>G
MANE Select: NM_001386140
dbSNP: rs566965111
Type: single nucleotide variant
Location: chr4:99594828 (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 285: the vitellogenin domain; 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.Thr285Met Uncertain significance ★ ⚠ same residue
MTTP p.Thr285= 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

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-thr285arg (accessed [today's date]).

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