Is AGAP1 p.Cys826= (c.2478C>T) pathogenic?

AGAP1 p.Cys826= (c.2478C>T) is classified Benign in AGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-02). Common (popmax 5.32%, eas) — too common for a highly-penetrant pathogenic allele.

AGAP1 p.Cys826=

Q: How common is AGAP1 p.Cys826= (c.2478C>T) in the general population?

AGAP1 p.Cys826= (c.2478C>T) is common (popmax 5.32%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2478C>T · rs78059134 · VCV2037562

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 5.32%, eas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.097	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.6	GERP -0.62
Overall
CADD	6.781	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.32% East Asian · 2,386/44,876 alleles

Filtering AF 5.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.07%

Overall 0.158% 2,544/1,613,980 alleles · common exomes 2,279/1,461,718 · genomes 265/152,262 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	5.32%	19
Remaining individualsnot grpmax-eligible	0.208%	481
Admixed American	0.0183%	5,457
Middle Eastern	0.0165%	6,060
South Asian	0.00988%	10,119
European (non-Finnish)	0.000593%	168,571

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: AGAP1
Protein: p.Cys826=
Coding: c.2478C>T
MANE Select: NM_001037131
dbSNP: rs78059134
Type: single nucleotide variant
Location: chr2:236124026 (GRCh38)
Gene constraint: LOEUF 0.366 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.01 · 2 PDB

Full AGAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AGAP1 p.Ala418Ser Uncertain significance ★★ ⚠ same type
AGAP1 p.Ala52Ser Uncertain significance ★★ ⚠ same type
AGAP1 p.Ala570Gly Uncertain significance ★★ same type
AGAP1 p.Ala809Ser Uncertain significance ★★ ⚠ same type
AGAP1 p.Arg14Trp Uncertain significance ★★ ⚠ same type
AGAP1 p.Arg313His Uncertain significance ★★ ⚠ same type
AGAP1 p.Arg696Trp Uncertain significance ★★ ⚠ same type
AGAP1 p.Arg770Cys 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/agap1-p-cys826 (accessed [today's date]).

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