Is RAB7A p.Val7= (c.21G>A) pathogenic?

RAB7A p.Val7= (c.21G>A) is classified Likely benign in RAB7A (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-09-24). Very rare (popmax 0.00924%, nfe); Associated with Inborn genetic diseases.

What condition is associated with RAB7A p.Val7= (c.21G>A)?

RAB7A p.Val7= (c.21G>A) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 2B, Charcot-Marie-Tooth disease (ClinVar).

How common is RAB7A p.Val7= (c.21G>A) in the general population?

RAB7A p.Val7= (c.21G>A) is very rare (popmax 0.00924%, nfe) (gnomAD).

RAB7A p.Val7=

c.21G>A · rs140857794 · VCV464094

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00924%, nfe)

Conditions

Inborn genetic diseases

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 0.35	GERP -0.68, phastCons 0.91
Overall
CADD	9.224	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00924% European (non-Finnish) · 109/1,179,400 alleles

Filtering AF 0.00783% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00728%

Overall 0.00719% 116/1,613,328 alleles · very rare exomes 114/1,461,180 · genomes 2/152,148 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00924%	10,820
Admixed American	0.005%	19,998
Remaining individualsnot grpmax-eligible	0.0032%	31,229
African / African-American	0.00267%	37,450

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: RAB7A
Protein: p.Val7=
Coding: c.21G>A
MANE Select: NM_004637
dbSNP: rs140857794
Type: single nucleotide variant
Location: chr3:128795388 (GRCh38)
Gene constraint: LOEUF 0.242 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.98 · 10 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease type 2B Charcot-Marie-Tooth disease

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-val7 (accessed [today's date]).

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