Is SRCAP p.Pro87Leu (c.260C>T) pathogenic?

SRCAP p.Pro87Leu (c.260C>T) is classified Uncertain significance in SRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-05). AlphaMissense: likely benign (0.0913); Very rare (popmax 0.0011%, sas).

How common is SRCAP p.Pro87Leu (c.260C>T) in the general population?

SRCAP p.Pro87Leu (c.260C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about SRCAP p.Pro87Leu (c.260C>T)?

AlphaMissense predicts likely benign (score 0.0913) — an in-silico prediction, not a clinical call.

SRCAP p.Pro87Leu

c.260C>T · VCV3615880

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0913 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
AlphaMissense	0.0913	likely benign
REVEL	0.307	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.4, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 3,462 bp · p 0.64 · regional, not allelic
Overall
CADD	22.3	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 0.0011% South Asian · 1/91,040 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000434% 7/1,613,388 alleles · very rare exomes 7/1,461,178 · genomes 0/152,210 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,592
South Asiangrpmax	0.0011%	91,040
European (non-Finnish)	0.000424%	235,896

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro87Leu
Coding: c.260C>T
MANE Select: NM_006662
Type: single nucleotide variant
Location: chr16:30704269 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

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

Similar variants

SRCAP p.Pro87Arg Uncertain significance ★ same residue
SRCAP p.Pro87= 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

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-pro87leu (accessed [today's date]).

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