Is RAB7A p.Ala76= (c.228C>G) pathogenic?

RAB7A p.Ala76= (c.228C>G) is classified Likely benign in RAB7A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-17). Absent from gnomAD v4.1; Associated with Charcot-Marie-Tooth disease type 2B.

What condition is associated with RAB7A p.Ala76= (c.228C>G)?

RAB7A p.Ala76= (c.228C>G) is associated with Charcot-Marie-Tooth disease type 2B (ClinVar).

How common is RAB7A p.Ala76= (c.228C>G) in the general population?

RAB7A p.Ala76= (c.228C>G) is absent from gnomAD v4.1 (gnomAD).

RAB7A p.Ala76=

Q: How is Autosomal dominant Charcot-Marie-Tooth disease type 2B inherited?

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

c.228C>G · VCV3653727

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Charcot-Marie-Tooth disease type 2B

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 1.8	phastCons 1
Overall
CADD	11.16	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RAB7A
Protein: p.Ala76=
Coding: c.228C>G
MANE Select: NM_004637
Type: single nucleotide variant
Location: chr3:128806419 (GRCh38)
Gene constraint: LOEUF 0.242 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.98 · 10 PDB
Residue 76: an α-helix

Full RAB7A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease type 2B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant Charcot-Marie-Tooth disease type 2B (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult

Similar variants

RAB7A p.Asn161Ile Pathogenic ★★ same condition
RAB7A p.Leu129Phe Pathogenic ★★ same condition
RAB7A p.Val162Met Pathogenic ★★ same condition
RAB7A c.*181G>A Uncertain significance ★★ same condition
RAB7A p.Arg69Gln Uncertain significance ★★ ⚠ same condition
RAB7A p.Ile169Thr Uncertain significance ★★ ⚠ same condition
RAB7A p.Leu56Pro Uncertain significance ★★ ⚠ same condition
RAB7A p.Ser155Asn 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/rab7a-p-ala76 (accessed [today's date]).

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