Is EXOC2 p.Phe213= (c.639C>T) pathogenic?

EXOC2 p.Phe213= (c.639C>T) is classified Likely benign in EXOC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-01). Ultra-rare (popmax 0.0438%, nfe).

How common is EXOC2 p.Phe213= (c.639C>T) in the general population?

EXOC2 p.Phe213= (c.639C>T) is ultra-rare (popmax 0.0438%, nfe) (gnomAD).

EXOC2 p.Phe213=

c.639C>T · rs147168208 · VCV1676001

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0438%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -3.2, phastCons 0.99
Overall
CADD	10.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0438% European (non-Finnish) · 517/1,179,372 alleles

Filtering AF 0.0407% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0395%

Overall 0.0349% 563/1,612,836 alleles · ultra-rare exomes 540/1,460,548 · genomes 23/152,288 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0438%	2,281
Remaining individualsnot grpmax-eligible	0.0272%	3,674
Finnishnot grpmax-eligible	0.0219%	4,573
African / African-American	0.00933%	10,716
Admixed American	0.00835%	11,971
South Asian	0.00331%	30,232

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.Phe213=
Coding: c.639C>T
MANE Select: NM_018303
dbSNP: rs147168208
Type: single nucleotide variant
Location: chr6:617733 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.82

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

Similar variants

HUS1B p.Ser213Leu Uncertain significance ★ ⚠ same residue
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

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-phe213 (accessed [today's date]).

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