Is EXOC7 p.Ser522= (c.1566C>T) pathogenic?

EXOC7 p.Ser522= (c.1566C>T) is classified Likely benign in EXOC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-01). Very rare (popmax 0.005%, amr); Associated with Inborn genetic diseases.

What condition is associated with EXOC7 p.Ser522= (c.1566C>T)?

EXOC7 p.Ser522= (c.1566C>T) is associated with Inborn genetic diseases (ClinVar).

How common is EXOC7 p.Ser522= (c.1566C>T) in the general population?

EXOC7 p.Ser522= (c.1566C>T) is very rare (popmax 0.005%, amr) (gnomAD).

EXOC7 p.Ser522=

c.1566C>T · VCV4251976

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

Inborn genetic diseases

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 -2.9	GERP -3.4
Overall
CADD	13.81	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,994 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000867% 14/1,613,958 alleles · very rare exomes 12/1,461,756 · genomes 2/152,202 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,998
Remaining individualsnot grpmax-eligible	0.0048%	20,827
South Asian	0.0022%	45,542
African / African-American	0.00133%	74,926
European (non-Finnish)	0.000424%	236,005

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: EXOC7
Protein: p.Ser522=
Coding: c.1566C>T
MANE Select: NM_001013839
Type: single nucleotide variant
Location: chr17:76085727 (GRCh38)
Gene constraint: LOEUF 0.76 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.41

Full EXOC7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EXOC7 p.Gln390Leu Uncertain significance ★★ ⚠ same condition
EXOC7 p.Val218Ile Uncertain significance ★★ ⚠ same condition
EXOC7 c.901+656A>G Likely benign ★★ same condition
EXOC7 p.Gln349Ter Pathogenic ★ same condition
EXOC7 c.127-5C>T Uncertain significance ★ same condition
EXOC7 c.417+2T>G Uncertain significance ★ same condition
EXOC7 c.901+728C>T Uncertain significance ★ ⚠ same condition
EXOC7 c.901+740C>T Uncertain significance ★ ⚠ same condition

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/exoc7-p-ser522 (accessed [today's date]).

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