Is RAB44 p.Ser778Pro (c.2332T>C) pathogenic?

RAB44 p.Ser778Pro (c.2332T>C) is classified Likely benign in RAB44 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-01). AlphaMissense: likely benign (0.0583); Rare (popmax 0.278%, amr).

How common is RAB44 p.Ser778Pro (c.2332T>C) in the general population?

RAB44 p.Ser778Pro (c.2332T>C) is rare (popmax 0.278%, amr) (gnomAD).

What do computational predictors say about RAB44 p.Ser778Pro (c.2332T>C)?

AlphaMissense predicts likely benign (score 0.0583) — an in-silico prediction, not a clinical call.

RAB44 p.Ser778Pro

c.2332T>C · rs534527709 · VCV2673060

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0583 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.278%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.0583	likely benign
SaProt	LLR -9.62	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.1	GERP -3
Regional constraint	o/e 0.84	unconstrained · MANE · 28 kb · p 2.6e-08 · regional, not allelic
Overall
CADD	0.081	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; SaProt is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.278% Admixed American · 106/38,090 alleles

Filtering AF 0.235% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.219%

Overall 0.122% 1,767/1,447,354 alleles · rare exomes 1,606/1,295,196 · genomes 161/152,158 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.278%	359
European (non-Finnish)	0.144%	694
Remaining individualsnot grpmax-eligible	0.109%	919
Middle Eastern	0.018%	5,550
African / African-American	0.0142%	7,023

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: RAB44
Protein: p.Ser778Pro
Coding: c.2332T>C
MANE Select: NM_001257357
dbSNP: rs534527709
Type: single nucleotide variant
Location: chr6:36722466 (GRCh38)
Gene constraint: LOEUF 1.029 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.25
Residue 778: the 'disordered' region

Full RAB44 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RAB44 p.Asp216Val Uncertain significance ★ same type
RAB44 p.Glu967Gln Uncertain significance ★ ⚠ same type
RAB44 p.Glu695= Likely benign ★ 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/rab44-p-ser778pro (accessed [today's date]).

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