Is EXOC2 p.Arg600Ser (c.1800A>T) pathogenic?

EXOC2 p.Arg600Ser (c.1800A>T) is classified Uncertain significance in EXOC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-25). AlphaMissense: likely benign (0.2541); Very rare (popmax 0.00118%, sas).

How common is EXOC2 p.Arg600Ser (c.1800A>T) in the general population?

EXOC2 p.Arg600Ser (c.1800A>T) is very rare (popmax 0.00118%, sas) (gnomAD).

What do computational predictors say about EXOC2 p.Arg600Ser (c.1800A>T)?

AlphaMissense predicts likely benign (score 0.2541) — an in-silico prediction, not a clinical call.

EXOC2 p.Arg600Ser

c.1800A>T · VCV4251817

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2541 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00118%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2541	likely benign
REVEL	0.21	benign-leaning
SaProt	LLR -4.45	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 -0.6	GERP -0.1
Regional constraint	o/e 0.83	unconstrained · MANE · 151 kb · p 2.5e-08 · regional, not allelic
Overall
CADD	17.9	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 0.00118% South Asian · 1/84,524 alleles

Filtering AF 0.000546% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000432%

Overall 0.000817% 13/1,592,082 alleles · very rare exomes 12/1,439,840 · genomes 1/152,242 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00118%	84,524
European (non-Finnish)	0.00102%	97,610

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: EXOC2
Protein: p.Arg600Ser
Coding: c.1800A>T
MANE Select: NM_018303
Type: single nucleotide variant
Location: chr6:562835 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.82
Residue 600: a UniProt-annotated variant site (in nedfach; decreased protein abundance; shows defective arl13b cilium membrane localization)

Full EXOC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EXOC2 p.Arg414His Uncertain significance ★★ ⚠ same type
EXOC2 p.Asp892Glu Uncertain significance ★★ ⚠ same type
EXOC2 p.Leu458= Likely benign ★★ same type
EXOC2 p.Phe153= Likely benign ★★ same type
EXOC2 p.Pro8= Likely benign ★★ same type
EXOC2 c.1443+10C>T Uncertain significance ★ same type
EXOC2 c.1932+4A>C Uncertain significance ★ same type
EXOC2 p.Ala228Thr 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/exoc2-p-arg600ser (accessed [today's date]).

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