Is SRCAP p.Pro1669Leu (c.5006C>T) pathogenic?

SRCAP p.Pro1669Leu (c.5006C>T) is classified Benign/Likely benign in SRCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-22). AlphaMissense: likely benign (0.0954); Low-frequency (popmax 1.22%, eas).

How common is SRCAP p.Pro1669Leu (c.5006C>T) in the general population?

SRCAP p.Pro1669Leu (c.5006C>T) is low-frequency (popmax 1.22%, eas) (gnomAD).

What do computational predictors say about SRCAP p.Pro1669Leu (c.5006C>T)?

AlphaMissense predicts likely benign (score 0.0954) — an in-silico prediction, not a clinical call.

SRCAP p.Pro1669Leu

c.5006C>T · rs189892751 · VCV318884

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0954 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.22%, eas)

Computational evidence

Protein change
AlphaMissense	0.0954	likely benign
REVEL	0.312	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 2.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 8,776 bp · p 0.24 · regional, not allelic
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.22% East Asian · 549/44,890 alleles

Filtering AF 1.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1%

Overall 0.043% 694/1,614,224 alleles · low-frequency exomes 568/1,461,894 · genomes 126/152,330 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.22%	82
Remaining individualsnot grpmax-eligible	0.101%	992
South Asian	0.0494%	2,024
African / African-American	0.0133%	7,505
Admixed American	0.01%	10,005
European (non-Finnish)	0.00178%	56,192

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.Pro1669Leu
Coding: c.5006C>T
MANE Select: NM_006662
dbSNP: rs189892751
Type: single nucleotide variant
Location: chr16:30724430 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1669: 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.Pro1669= Likely benign ★★ same residue
SRCAP p.Arg2329Ter Pathogenic/Likely pathogenic ★★ same type
SRCAP p.Arg2435Ter Pathogenic/Likely pathogenic ★★ same type
SRCAP p.Arg2444Ter Pathogenic ★★ same type
SRCAP p.Arg2718Ter Pathogenic/Likely pathogenic ★★ same type
SRCAP p.Arg2748Ter Pathogenic ★★ same type
SRCAP p.Gln2407Ter Pathogenic ★★ same type
SRCAP p.Gln2419Ter 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-pro1669leu (accessed [today's date]).

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