Is MMACHC c.*467G>A pathogenic?

MMACHC c.467G>A is classified Uncertain significance in MMACHC (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Rare (popmax 0.485%, afr); Associated with Disorders of Intracellular Cobalamin Metabolism.

What condition is associated with MMACHC c.*467G>A?

MMACHC c.*467G>A is associated with Disorders of Intracellular Cobalamin Metabolism (ClinVar).

How common is MMACHC c.*467G>A in the general population?

MMACHC c.*467G>A is rare (popmax 0.485%, afr) (gnomAD).

MMACHC c.*467G>A

rs551671089 · VCV875471

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.485%, afr)

Conditions

Disorders of Intracellular Cobalamin Metabolism

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 -0.31	GERP 0.18
Overall
CADD	2.154	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.485% African / African-American · 201/41,432 alleles

Filtering AF 0.43% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.409%

Overall 0.128% 207/162,208 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.485%	206
Remaining individualsnot grpmax-eligible	0.0778%	1,285
Admixed American	0.0243%	4,115

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: MMACHC
Coding: c.*467G>A
MANE Select: NM_015506
dbSNP: rs551671089
Type: single nucleotide variant
Location: chr1:45509682 (GRCh38)
Gene constraint: LOEUF 1.162 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.41 · 7 PDB

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

Disease context

Disorders of Intracellular Cobalamin Metabolism — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MMACHC c.-123A>T Uncertain significance ★★ same condition
MMACHC c.*201G>T Uncertain significance ★★ same condition
MMACHC p.Glu106Lys Uncertain significance ★★ ⚠ same condition
MMACHC p.Val135Leu Uncertain significance ★★ ⚠ same condition
MMACHC c.*1144A>T Likely benign ★★ same condition
MMACHC c.*1260G>A Benign ★★ same condition
MMACHC c.*1362G>A Benign ★★ same condition
MMACHC c.*1585G>C Benign ★★ 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/mmachc-c-star-467g-a (accessed [today's date]).

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