Is SRGAP1 p.Asp789= (c.2367C>T) pathogenic?

SRGAP1 p.Asp789= (c.2367C>T) is classified Likely benign in SRGAP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-04). Very rare (popmax 0.00667%, amr); Associated with SRGAP1-related disorder.

What condition is associated with SRGAP1 p.Asp789= (c.2367C>T)?

SRGAP1 p.Asp789= (c.2367C>T) is associated with SRGAP1-related disorder (ClinVar).

How common is SRGAP1 p.Asp789= (c.2367C>T) in the general population?

SRGAP1 p.Asp789= (c.2367C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

SRGAP1 p.Asp789=

c.2367C>T · rs766056847 · VCV3044353

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Conditions

SRGAP1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -11	GERP -5.6
Overall
CADD	5.509	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/60,000 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00217% 35/1,614,038 alleles · very rare exomes 30/1,461,838 · genomes 5/152,200 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	15,000
African / African-American	0.00267%	37,464
European (non-Finnish)	0.00237%	42,144
South Asian	0.0011%	91,082

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.Asp789=
Coding: c.2367C>T
MANE Select: NM_020762
dbSNP: rs766056847
Type: single nucleotide variant
Location: chr12:64126119 (GRCh38)
Gene constraint: LOEUF 0.47 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.49
Residue 789: 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.Arg760Lys 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

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-asp789 (accessed [today's date]).

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