Is SRGAP1 p.Arg900Gly (c.2698C>G) pathogenic?

SRGAP1 p.Arg900Gly (c.2698C>G) is classified Uncertain significance in SRGAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-11). AlphaMissense: likely benign (0.1265); Very rare (popmax 0.00534%, afr); Associated with SRGAP1-related disorder.

What condition is associated with SRGAP1 p.Arg900Gly (c.2698C>G)?

SRGAP1 p.Arg900Gly (c.2698C>G) is associated with SRGAP1-related disorder (ClinVar).

How common is SRGAP1 p.Arg900Gly (c.2698C>G) in the general population?

SRGAP1 p.Arg900Gly (c.2698C>G) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about SRGAP1 p.Arg900Gly (c.2698C>G)?

AlphaMissense predicts likely benign (score 0.1265) — an in-silico prediction, not a clinical call.

SRGAP1 p.Arg900Gly

c.2698C>G · rs768091956 · VCV2632760

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1265 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

SRGAP1-related disorder

Computational evidence

Protein change
AlphaMissense	0.1265	likely benign
REVEL	0.19	benign-leaning
SaProt	LLR -4.85	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 7.6	GERP 2.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 15 kb · p 0.13 · regional, not allelic
Overall
CADD	24.3	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 0.00534% African / African-American · 4/74,936 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,614,076 alleles · very rare exomes 1/1,461,890 · genomes 3/152,186 · 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.Arg900Gly
Coding: c.2698C>G
MANE Select: NM_020762
dbSNP: rs768091956
Type: single nucleotide variant
Location: chr12:64128018 (GRCh38)
Gene constraint: LOEUF 0.47 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.49
Residue 900: the 'disordered' region

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

Disease context

SRGAP1-related disorder

Similar variants

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
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-arg900gly (accessed [today's date]).

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