Is MTTP p.Pro836= (c.2508A>G) pathogenic?

MTTP p.Pro836= (c.2508A>G) is classified Likely benign in MTTP (ClinVar, Single submitter, 2 submitters; last evaluated 2024-04-04). Very rare (popmax 0.000848%, nfe); Associated with abetalipoproteinemia.

What condition is associated with MTTP p.Pro836= (c.2508A>G)?

MTTP p.Pro836= (c.2508A>G) is associated with abetalipoproteinemia (ClinVar).

How common is MTTP p.Pro836= (c.2508A>G) in the general population?

MTTP p.Pro836= (c.2508A>G) is very rare (popmax 0.000848%, nfe) (gnomAD).

How is Abetalipoproteinemia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MTTP p.Pro836=

c.2508A>G · rs1432922772 · VCV1630557

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000848%, nfe)

Conditions

abetalipoproteinemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.3	GERP -3.1
Overall
CADD	0.031	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000848% European (non-Finnish) · 10/1,179,880 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.00062% 10/1,613,868 alleles · very rare exomes 9/1,461,728 · genomes 1/152,140 · 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.Pro836=
Coding: c.2508A>G
MANE Select: NM_001386140
dbSNP: rs1432922772
Type: single nucleotide variant
Location: chr4:99621226 (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 836: a β-strand

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

Disease context

abetalipoproteinemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Abetalipoproteinemia (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

MTTP c.1067+1G>C Likely pathogenic ★★ same condition
MTTP c.1769+2T>C Pathogenic/Likely pathogenic ★★ same condition
MTTP c.1867+1G>A Pathogenic ★★ same condition
MTTP c.1867+5G>A Pathogenic/Likely pathogenic ★★ same condition
MTTP c.1868-2A>G Likely pathogenic ★★ same condition
MTTP c.2342+1G>A Pathogenic ★★ same condition
MTTP c.502-1G>C Likely pathogenic ★★ same condition
MTTP c.502-2A>G Likely pathogenic ★★ 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-pro836 (accessed [today's date]).

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