Is SRGAP1 p.Arg760Lys (c.2279G>A) pathogenic?

SRGAP1 p.Arg760Lys (c.2279G>A) is classified Uncertain significance in SRGAP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely benign (0.2973); Very rare (popmax 0.00102%, nfe); Associated with SRGAP1-related disorder.

What condition is associated with SRGAP1 p.Arg760Lys (c.2279G>A)?

SRGAP1 p.Arg760Lys (c.2279G>A) is associated with SRGAP1-related disorder (ClinVar).

How common is SRGAP1 p.Arg760Lys (c.2279G>A) in the general population?

SRGAP1 p.Arg760Lys (c.2279G>A) is very rare (popmax 0.00102%, nfe) (gnomAD).

What do computational predictors say about SRGAP1 p.Arg760Lys (c.2279G>A)?

AlphaMissense predicts likely benign (score 0.2973) — an in-silico prediction, not a clinical call.

SRGAP1 p.Arg760Lys

c.2279G>A · rs1446124416 · VCV3031096

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2973 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

SRGAP1-related disorder

Computational evidence

Protein change
AlphaMissense	0.2973	likely benign
REVEL	0.243	benign-leaning
SaProt	LLR -7.62	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 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 281 kb · p 2.2e-09 · regional, not allelic
Overall
CADD	26.1	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

Grpmax group 0.00102% European (non-Finnish) · 12/1,180,028 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000743% 12/1,614,208 alleles · very rare exomes 12/1,461,870 · genomes 0/152,338 · joint denominator

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: SRGAP1
Protein: p.Arg760Lys
Coding: c.2279G>A
MANE Select: NM_020762
dbSNP: rs1446124416
Type: single nucleotide variant
Location: chr12:64126031 (GRCh38)
Gene constraint: LOEUF 0.47 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.49
Residue 760: the sh3 domain

Full SRGAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

SRGAP1-related disorder

Similar variants

SRGAP1 p.Arg900Gly Uncertain significance ★★ ⚠ same condition
SRGAP1 p.Arg54Gln Uncertain significance ⚠ same condition
SRGAP1 p.Asp267Tyr Uncertain significance ⚠ same condition
SRGAP1 p.Ser2Tyr Uncertain significance ⚠ same condition
SRGAP1 c.1323+6C>T Likely benign same condition
SRGAP1 c.427-4A>T Likely benign same condition
SRGAP1 p.Ala185= Likely benign same condition
SRGAP1 p.Arg312= Likely benign same condition

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/srgap1-p-arg760lys (accessed [today's date]).

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