Is SRGAP2 p.His307Pro (c.920A>C) pathogenic?

SRGAP2 p.His307Pro (c.920A>C) is classified Uncertain significance in SRGAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-01). AlphaMissense: likely pathogenic (0.9541); Absent from gnomAD v4.1.

How common is SRGAP2 p.His307Pro (c.920A>C) in the general population?

SRGAP2 p.His307Pro (c.920A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SRGAP2 p.His307Pro (c.920A>C)?

AlphaMissense predicts likely pathogenic (score 0.9541) — an in-silico prediction, not a clinical call.

SRGAP2 p.His307Pro

c.920A>C · rs1350526469 · VCV623713

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9541 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9541	likely pathogenic
REVEL	0.258	benign-leaning
SaProt	LLR -15.65	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.12	constrained · MANE · 7,955 bp · p 3.1e-07 · regional, not allelic
Overall
CADD	27.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SRGAP2
Protein: p.His307Pro
Coding: c.920A>C
MANE Select: NM_015326
dbSNP: rs1350526469
Type: single nucleotide variant
Location: chr1:206401509 (GRCh38)
Gene constraint: LOEUF 0.556 · pLI 0.87 (gnomAD)
Structure: AlphaFold pLDDT 72.59 · 6 PDB
Residue 307: the f-bar domain; an α-helix

Full SRGAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SRGAP2 p.Arg235His Uncertain significance ★ ⚠ same type
SRGAP2 p.Glu480Asp Uncertain significance ★ ⚠ same type
SRGAP2 p.Pro339Ser 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/srgap2-p-his307pro (accessed [today's date]).

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