Is SRCAP p.Phe1867del (c.5598_5600del) pathogenic?

SRCAP p.Phe1867del (c.55985600del) is classified Benign/Likely benign in SRCAP (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-05-12). Rare (popmax 0.59%, sas).

How common is SRCAP p.Phe1867del (c.5598_5600del) in the general population?

SRCAP p.Phe1867del (c.5598_5600del) is rare (popmax 0.59%, sas) (gnomAD).

SRCAP p.Phe1867del

c.5598_5600del · rs565950672 · VCV318888

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.59%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Overall
CADD	17.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.59% South Asian · 537/91,082 alleles

Filtering AF 0.548% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.532%

Overall 0.0649% 1,048/1,614,022 alleles · rare exomes 962/1,461,742 · genomes 86/152,280 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.59%	170
Middle Eastern	0.478%	209
Admixed American	0.115%	870
Remaining individualsnot grpmax-eligible	0.096%	1,042
European (non-Finnish)	0.0278%	3,597
African / African-American	0.0227%	4,415
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,399
Finnishnot grpmax-eligible	0.00469%	21,333
East Asian	0.00223%	44,884

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: SRCAP
Protein: p.Phe1867del
Coding: c.5598_5600del
MANE Select: NM_006662
dbSNP: rs565950672
Type: Deletion
Location: chr16:30725022 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1867: the 'disordered' region; a UniProt-annotated variant site (in dehmba)

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

Similar variants

SRCAP p.Pro2459fs Pathogenic/Likely pathogenic ★★ same type
SRCAP p.Pro2461fs Pathogenic ★★ same type
SRCAP p.Ser2463fs Pathogenic ★★ same type
SRCAP p.Thr572del Uncertain significance ★★ same type
SRCAP p.Val1012del Uncertain significance ★★ same type
SRCAP c.1187_1228+67del Likely pathogenic ★ same type
SRCAP c.1319del Pathogenic ★ same type
SRCAP c.2298_2300+3del Pathogenic ★ 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/srcap-p-phe1867del (accessed [today's date]).

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