Is SRCAP p.Thr2784Pro (c.8350A>C) pathogenic?

SRCAP p.Thr2784Pro (c.8350A>C) is classified Benign/Likely benign in SRCAP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-06-05). AlphaMissense: likely benign (0.0788); Low-frequency (popmax 1.13%, afr).

How common is SRCAP p.Thr2784Pro (c.8350A>C) in the general population?

SRCAP p.Thr2784Pro (c.8350A>C) is low-frequency (popmax 1.13%, afr) (gnomAD).

What do computational predictors say about SRCAP p.Thr2784Pro (c.8350A>C)?

AlphaMissense predicts likely benign (score 0.0788) — an in-silico prediction, not a clinical call.

SRCAP p.Thr2784Pro

c.8350A>C · rs73538429 · VCV318900

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0788 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.13%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0788	likely benign
REVEL	0.235	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -1, phastCons 0.98
Regional constraint	o/e 1.06	unconstrained · MANE · 2,598 bp · p 0.058 · regional, not allelic
Overall
CADD	16.22	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 1.13% African / African-American · 820/72,856 alleles

Filtering AF 1.06% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.04%

Overall 0.0564% 874/1,550,188 alleles · low-frequency exomes 421/1,397,956 · genomes 453/152,232 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.13%	89
Remaining individualsnot grpmax-eligible	0.0537%	1,863
Middle Eastern	0.0349%	2,867
Admixed American	0.0277%	3,611
South Asian	0.00124%	80,366
European (non-Finnish)	0.000435%	229,863

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.Thr2784Pro
Coding: c.8350A>C
MANE Select: NM_006662
dbSNP: rs73538429
Type: single nucleotide variant
Location: chr16:30738390 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2784: the 'disordered' region; a UniProt-annotated variant site (in dehmba); a UniProt-annotated variant site (in flhs)

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

Similar variants

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
SRCAP p.Gln2665Ter Pathogenic/Likely 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-thr2784pro (accessed [today's date]).

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