Is RAB5C p.Pro207Ser (c.619C>T) pathogenic?

RAB5C p.Pro207Ser (c.619C>T) is classified Uncertain significance in RAB5C (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-27). AlphaMissense: likely benign (0.0695); Very rare (popmax 0.00893%, eas); Associated with Inborn genetic diseases.

What condition is associated with RAB5C p.Pro207Ser (c.619C>T)?

RAB5C p.Pro207Ser (c.619C>T) is associated with Inborn genetic diseases (ClinVar).

How common is RAB5C p.Pro207Ser (c.619C>T) in the general population?

RAB5C p.Pro207Ser (c.619C>T) is very rare (popmax 0.00893%, eas) (gnomAD).

What do computational predictors say about RAB5C p.Pro207Ser (c.619C>T)?

AlphaMissense predicts likely benign (score 0.0695) — an in-silico prediction, not a clinical call.

RAB5C p.Pro207Ser

c.619C>T · rs782112616 · VCV2292104

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0695 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00893%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0695	likely benign
REVEL	0.162	moderately benign-leaning
SaProt	LLR -6.42	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.1, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 2,984 bp · p 0.0012 · regional, not allelic
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00893% East Asian · 4/44,772 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000274% 4/1,457,626 alleles · very rare

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: RAB5C
Protein: p.Pro207Ser
Coding: c.619C>T
MANE Select: NM_004583
dbSNP: rs782112616
Type: single nucleotide variant
Location: chr17:42125815 (GRCh38)
Gene constraint: LOEUF 0.41 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 85.39 · 1 PDB
Residue 207: the 'disordered' region

Full RAB5C 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

Similar variants

RAB5C p.Gln80Arg Likely pathogenic ★★ same condition
RAB5C p.Ala132Thr Uncertain significance ★ ⚠ same condition
RAB5C p.Ala2Thr Uncertain significance ★ ⚠ same condition
RAB5C p.Ala7Thr Uncertain significance ★ ⚠ same condition
RAB5C p.Ala7Val Uncertain significance ★ ⚠ same condition
RAB5C p.Arg198Gln Uncertain significance ★ ⚠ same condition
RAB5C p.Arg210Gln Uncertain significance ★ ⚠ same condition
RAB5C p.Asn105Ser 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/rab5c-p-pro207ser (accessed [today's date]).

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