Is SRGAP1 p.Leu623Phe (c.1869G>T) pathogenic?

SRGAP1 p.Leu623Phe (c.1869G>T) is classified Uncertain significance in SRGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-27). AlphaMissense: likely benign (0.1826); No allele count reported in gnomAD v4.1 (AN 1,603,486).

How common is SRGAP1 p.Leu623Phe (c.1869G>T) in the general population?

SRGAP1 p.Leu623Phe (c.1869G>T) is no allele count reported in gnomAD v4.1 (AN 1,603,486) (gnomAD).

What do computational predictors say about SRGAP1 p.Leu623Phe (c.1869G>T)?

AlphaMissense predicts likely benign (score 0.1826) — an in-silico prediction, not a clinical call.

SRGAP1 p.Leu623Phe

c.1869G>T · rs2136612301 · VCV2541500

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1826 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,603,486)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1826	likely benign
REVEL	0.319	indeterminate
SaProt	LLR -9.36	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 281 kb · p 2.2e-09 · regional, not allelic
Overall
CADD	23.7	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

No allele count reported in gnomAD v4.1 (AN 1,603,486). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SRGAP1
Protein: p.Leu623Phe
Coding: c.1869G>T
MANE Select: NM_020762
dbSNP: rs2136612301
Type: single nucleotide variant
Location: chr12:64108987 (GRCh38)
Gene constraint: LOEUF 0.47 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.49
Residue 623: the rho-gap domain

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

Similar variants

SRGAP1 p.Arg900Gly Uncertain significance ★★ ⚠ same type
SRGAP1 c.2225-7G>A Likely benign ★★ same type
SRGAP1 p.Asn786= Benign ★★ same type
SRGAP1 p.His875Arg Benign ★★ same type
SRGAP1 p.His924= Benign ★★ same type
SRGAP1 p.Ile371= Benign ★★ same type
SRGAP1 p.Leu49= Benign/Likely benign ★★ same type
SRGAP1 p.Leu953Val Benign ★★ same type

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-leu623phe (accessed [today's date]).

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