Is SRGAP2 p.Glu480Asp (c.1440A>T) pathogenic?

SRGAP2 p.Glu480Asp (c.1440A>T) is classified Uncertain significance in SRGAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-01). AlphaMissense: likely benign (0.1566); Absent from gnomAD v4.1.

How common is SRGAP2 p.Glu480Asp (c.1440A>T) in the general population?

SRGAP2 p.Glu480Asp (c.1440A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SRGAP2 p.Glu480Asp (c.1440A>T)?

AlphaMissense predicts likely benign (score 0.1566) — an in-silico prediction, not a clinical call.

SRGAP2 p.Glu480Asp

c.1440A>T · rs2528284116 · VCV2639858

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1566 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1566	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -6.17	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 0.24, phastCons 1
Regional constraint	o/e 1.28	unconstrained · MANE · 46 kb · p 6.5e-08 · regional, not allelic
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Glu480Asp
Coding: c.1440A>T
MANE Select: NM_015326
dbSNP: rs2528284116
Type: single nucleotide variant
Location: chr1:206415972 (GRCh38)
Gene constraint: LOEUF 0.556 · pLI 0.87 (gnomAD)
Structure: AlphaFold pLDDT 72.59 · 6 PDB

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.His307Pro 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-glu480asp (accessed [today's date]).

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