Is AGAP1 p.Ser320Pro (c.958T>C) pathogenic?

AGAP1 p.Ser320Pro (c.958T>C) is classified Conflicting classifications of pathogenicity in AGAP1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-09-04). AlphaMissense: likely pathogenic (0.6559); Ultra-rare (popmax 0.0165%, mid).

How common is AGAP1 p.Ser320Pro (c.958T>C) in the general population?

AGAP1 p.Ser320Pro (c.958T>C) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about AGAP1 p.Ser320Pro (c.958T>C)?

AlphaMissense predicts likely pathogenic (score 0.6559) — an in-silico prediction, not a clinical call.

AGAP1 p.Ser320Pro

c.958T>C · rs202230563 · VCV2255562

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6559 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6559	likely pathogenic
REVEL	0.524	indeterminate
SaProt	LLR -9.86	tolerated
⇒ AlphaMissense calls this damaging; SaProt 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 7.8	GERP 2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 546 kb · p 0.00065 · regional, not allelic
Overall
CADD	28.4	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 0.0165% Middle Eastern · 1/6,066 alleles

Filtering AF 0.00291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0026%

Overall 0.0192% 309/1,610,074 alleles · ultra-rare exomes 277/1,457,950 · genomes 32/152,124 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.771%	130
Remaining individualsnot grpmax-eligible	0.053%	1,888
Middle Easterngrpmax	0.0165%	6,066
European (non-Finnish)	0.00382%	26,200
Admixed American	0.0017%	58,656
African / African-American	0.00134%	74,382

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser320Pro
Coding: c.958T>C
MANE Select: NM_001037131
dbSNP: rs202230563
Type: single nucleotide variant
Location: chr2:235807239 (GRCh38)
Gene constraint: LOEUF 0.366 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.01 · 2 PDB
Residue 320: the 'disordered' region

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-ser320pro (accessed [today's date]).

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