Is AGAP1 p.Pro827Ser (c.2479C>T) pathogenic?

AGAP1 p.Pro827Ser (c.2479C>T) is classified Uncertain significance in AGAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-19). AlphaMissense: likely benign (0.1503); Rare (popmax 0.462%, mid).

How common is AGAP1 p.Pro827Ser (c.2479C>T) in the general population?

AGAP1 p.Pro827Ser (c.2479C>T) is rare (popmax 0.462%, mid) (gnomAD).

What do computational predictors say about AGAP1 p.Pro827Ser (c.2479C>T)?

AlphaMissense predicts likely benign (score 0.1503) — an in-silico prediction, not a clinical call.

AGAP1 p.Pro827Ser

c.2479C>T · rs140144664 · VCV2886000

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1503 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.462%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1503	likely benign
REVEL	0.422	indeterminate
SaProt	LLR -12.13	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.5	GERP 1.5, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 75 kb · p 0.03 · regional, not allelic
Overall
CADD	25.8	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 0.462% Middle Eastern · 28/6,060 alleles

Filtering AF 0.328% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.283%

Overall 0.00936% 151/1,614,064 alleles · rare exomes 131/1,461,804 · genomes 20/152,260 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.462%	216
Remaining individualsnot grpmax-eligible	0.0352%	2,841
African / African-American	0.0147%	6,821
South Asian	0.0143%	7,005
European (non-Finnish)	0.00653%	15,325

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.Pro827Ser
Coding: c.2479C>T
MANE Select: NM_001037131
dbSNP: rs140144664
Type: single nucleotide variant
Location: chr2:236124027 (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-pro827ser (accessed [today's date]).

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