Is MTTP p.Arg772Cys (c.2314C>T) pathogenic?

MTTP p.Arg772Cys (c.2314C>T) is classified Uncertain significance in MTTP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-08). AlphaMissense: likely pathogenic (0.8501); Very rare (popmax 0.00267%, afr).

How common is MTTP p.Arg772Cys (c.2314C>T) in the general population?

MTTP p.Arg772Cys (c.2314C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about MTTP p.Arg772Cys (c.2314C>T)?

AlphaMissense predicts likely pathogenic (score 0.8501) — an in-silico prediction, not a clinical call.

MTTP p.Arg772Cys

c.2314C>T · rs1376017096 · VCV2157988

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8501 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8501	likely pathogenic · top 10% in MTTP
REVEL	0.633	indeterminate
SaProt	LLR -14.05	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 48 kb · p 0.00018 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00267% African / African-American · 2/74,860 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000496% 8/1,613,348 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,430
East Asian	0.00223%	44,840
European (non-Finnish)	0.000424%	235,915

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.Arg772Cys
Coding: c.2314C>T
MANE Select: NM_001386140
dbSNP: rs1376017096
Type: single nucleotide variant
Location: chr4:99619070 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.73 · 2 PDB

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

Similar variants

MTTP p.Arg772His 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
MTTP c.2342+1G>A 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-arg772cys (accessed [today's date]).

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