Is SRGAP1 p.His722= (c.2166C>T) pathogenic?

SRGAP1 p.His722= (c.2166C>T) is classified Likely benign in SRGAP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-28). Very rare (popmax 0.00989%, sas); Associated with SRGAP1-related disorder.

What condition is associated with SRGAP1 p.His722= (c.2166C>T)?

SRGAP1 p.His722= (c.2166C>T) is associated with SRGAP1-related disorder (ClinVar).

How common is SRGAP1 p.His722= (c.2166C>T) in the general population?

SRGAP1 p.His722= (c.2166C>T) is very rare (popmax 0.00989%, sas) (gnomAD).

SRGAP1 p.His722=

c.2166C>T · VCV3353046

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00989%, 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 -6.9	GERP -5.2
Overall
CADD	7.086	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00989% South Asian · 9/90,970 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00376%

Overall 0.00446% 72/1,613,458 alleles · very rare exomes 67/1,461,276 · genomes 5/152,182 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00989%	10,108
European (non-Finnish)	0.00509%	19,662
East Asian	0.00223%	44,856
Admixed American	0.00167%	59,944
Remaining individualsnot grpmax-eligible	0.0016%	62,454

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.His722=
Coding: c.2166C>T
MANE Select: NM_020762
Type: single nucleotide variant
Location: chr12:64115835 (GRCh38)
Gene constraint: LOEUF 0.47 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.49

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-his722 (accessed [today's date]).

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