Is EXOC2 p.Val587Ile (c.1759G>A) pathogenic?

EXOC2 p.Val587Ile (c.1759G>A) is classified Benign in EXOC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-29). AlphaMissense: likely benign (0.0708); Low-frequency (popmax 3.18%, afr).

How common is EXOC2 p.Val587Ile (c.1759G>A) in the general population?

EXOC2 p.Val587Ile (c.1759G>A) is low-frequency (popmax 3.18%, afr) (gnomAD).

What do computational predictors say about EXOC2 p.Val587Ile (c.1759G>A)?

AlphaMissense predicts likely benign (score 0.0708) — an in-silico prediction, not a clinical call.

EXOC2 p.Val587Ile

c.1759G>A · rs61744205 · VCV712583

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0708 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.18%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0708	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -7.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.1	GERP -0.39, phastCons 0.98
Regional constraint	o/e 0.83	unconstrained · MANE · 151 kb · p 2.5e-08 · regional, not allelic
Overall
CADD	14.49	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.18% African / African-American · 2,386/75,012 alleles

Filtering AF 3.07% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.03%

Overall 0.172% 2,774/1,614,062 alleles · low-frequency exomes 1,466/1,461,802 · genomes 1,308/152,260 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.18%	31
Remaining individualsnot grpmax-eligible	0.205%	488
Admixed American	0.19%	526
Middle Eastern	0.033%	3,031
European (non-Finnish)	0.0115%	8,676
East Asian	0.00668%	14,961
South Asian	0.00549%	18,211

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.Val587Ile
Coding: c.1759G>A
MANE Select: NM_018303
dbSNP: rs61744205
Type: single nucleotide variant
Location: chr6:564063 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.82
Residue 587: 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-val587ile (accessed [today's date]).

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