Is SRGAP1 p.Ala185= (c.555C>T) pathogenic?

SRGAP1 p.Ala185= (c.555C>T) is classified Likely benign in SRGAP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-03-02). Ultra-rare (popmax 0.0626%, sas); Associated with SRGAP1-related disorder.

What condition is associated with SRGAP1 p.Ala185= (c.555C>T)?

SRGAP1 p.Ala185= (c.555C>T) is associated with SRGAP1-related disorder (ClinVar).

How common is SRGAP1 p.Ala185= (c.555C>T) in the general population?

SRGAP1 p.Ala185= (c.555C>T) is ultra-rare (popmax 0.0626%, sas) (gnomAD).

SRGAP1 p.Ala185=

c.555C>T · rs757099301 · VCV3031469

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0626%, sas)

Conditions

SRGAP1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.9	GERP -3.5
Overall
CADD	6.595	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0626% South Asian · 57/91,058 alleles

Filtering AF 0.0496% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0449%

Overall 0.00452% 73/1,613,316 alleles · ultra-rare exomes 68/1,461,514 · genomes 5/151,802 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0626%	1,598
Remaining individualsnot grpmax-eligible	0.0048%	20,823
European (non-Finnish)	0.0011%	90,753

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.Ala185=
Coding: c.555C>T
MANE Select: NM_020762
dbSNP: rs757099301
Type: single nucleotide variant
Location: chr12:64042855 (GRCh38)
Gene constraint: LOEUF 0.47 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.49
Residue 185: the f-bar 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.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-ala185 (accessed [today's date]).

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