Is MTTP p.Arg32Trp (c.94C>T) pathogenic?

MTTP p.Arg32Trp (c.94C>T) is classified Uncertain significance in MTTP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-23). AlphaMissense: likely benign (0.1571); Very rare (popmax 0.00167%, amr).

How common is MTTP p.Arg32Trp (c.94C>T) in the general population?

MTTP p.Arg32Trp (c.94C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about MTTP p.Arg32Trp (c.94C>T)?

AlphaMissense predicts likely benign (score 0.1571) — an in-silico prediction, not a clinical call.

MTTP p.Arg32Trp

c.94C>T · VCV4967888

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1571 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1571	likely benign
REVEL	0.256	benign-leaning
SaProt	LLR -10.24	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.59 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.6	GERP -1.5, phastCons 0.98
Regional constraint	o/e 0.89	unconstrained · MANE · 48 kb · p 0.00018 · regional, not allelic
Overall
CADD	26.3	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 0.00167% Admixed American · 1/59,990 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.00031% 5/1,613,910 alleles · very rare exomes 3/1,461,842 · genomes 2/152,068 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,990
African / African-American	0.00134%	74,878
South Asian	0.0011%	91,064
European (non-Finnish)	0.000169%	589,991

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.Arg32Trp
Coding: c.94C>T
MANE Select: NM_001386140
Type: single nucleotide variant
Location: chr4:99581937 (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 32: the vitellogenin domain

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

Similar variants

MTTP p.Arg32= Likely benign ★★ same residue
MTTP p.Arg32Gln Benign/Likely benign ★★ same residue
MTTP p.Arg32Gly 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

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-arg32trp (accessed [today's date]).

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