Is EXOC2 p.Phe726Val (c.2176T>G) pathogenic?

EXOC2 p.Phe726Val (c.2176T>G) is classified Uncertain significance in EXOC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-30). AlphaMissense: likely benign (0.2855); Absent from gnomAD v4.1.

How common is EXOC2 p.Phe726Val (c.2176T>G) in the general population?

EXOC2 p.Phe726Val (c.2176T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EXOC2 p.Phe726Val (c.2176T>G)?

AlphaMissense predicts likely benign (score 0.2855) — an in-silico prediction, not a clinical call.

EXOC2 p.Phe726Val

c.2176T>G · rs2532830515 · VCV2329950

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2855 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2855	likely benign
REVEL	0.149	moderately benign-leaning
SaProt	LLR -4.22	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 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 151 kb · p 2.5e-08 · regional, not allelic
Overall
CADD	23.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EXOC2
Protein: p.Phe726Val
Coding: c.2176T>G
MANE Select: NM_018303
dbSNP: rs2532830515
Type: single nucleotide variant
Location: chr6:549237 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.82
Residue 726: 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-phe726val (accessed [today's date]).

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