Is RAB8A p.Ser17Thr (c.49T>A) pathogenic?

RAB8A p.Ser17Thr (c.49T>A) is classified Uncertain significance in RAB8A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). AlphaMissense: likely pathogenic (0.8065); Very rare (popmax 0.00267%, afr).

How common is RAB8A p.Ser17Thr (c.49T>A) in the general population?

RAB8A p.Ser17Thr (c.49T>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about RAB8A p.Ser17Thr (c.49T>A)?

AlphaMissense predicts likely pathogenic (score 0.8065) — an in-silico prediction, not a clinical call.

RAB8A p.Ser17Thr

c.49T>A · VCV4575075

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8065 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8065	likely pathogenic
REVEL	0.649	pathogenic-leaning
SaProt	LLR -11.37	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 105 bp · p 0.0097 · regional, not allelic
Overall
CADD	29.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00267% African / African-American · 2/74,912 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,613,900 alleles · very rare exomes 1/1,461,716 · genomes 1/152,184 · 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: RAB8A
Protein: p.Ser17Thr
Coding: c.49T>A
MANE Select: NM_005370
Type: single nucleotide variant
Location: chr19:16111950 (GRCh38)
Gene constraint: LOEUF 0.34 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.70 · 21 PDB
Residue 17: a binding site

Full RAB8A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RAB8A c.124+2T>G Uncertain significance ★ same type
RAB8A p.Arg71Gln Uncertain significance ★ ⚠ same type
RAB8A p.Asp31Glu Uncertain significance ★ ⚠ same type
RAB8A p.Ile50Leu Uncertain significance ★ ⚠ same type
RAB8A p.Ile50Thr Uncertain significance ★ ⚠ same type
RAB8A p.Thr75Met Uncertain significance ★ ⚠ same type

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/rab8a-p-ser17thr (accessed [today's date]).

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