Is SRCAP p.Pro278Arg (c.833C>G) pathogenic?

SRCAP p.Pro278Arg (c.833C>G) is classified Likely benign in SRCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-19). AlphaMissense: likely benign (0.1053); Ultra-rare (popmax 0.0423%, eas); Associated with Inborn genetic diseases.

What condition is associated with SRCAP p.Pro278Arg (c.833C>G)?

SRCAP p.Pro278Arg (c.833C>G) is associated with Inborn genetic diseases (ClinVar).

How common is SRCAP p.Pro278Arg (c.833C>G) in the general population?

SRCAP p.Pro278Arg (c.833C>G) is ultra-rare (popmax 0.0423%, eas) (gnomAD).

What do computational predictors say about SRCAP p.Pro278Arg (c.833C>G)?

AlphaMissense predicts likely benign (score 0.1053) — an in-silico prediction, not a clinical call.

SRCAP p.Pro278Arg

c.833C>G · rs759291172 · VCV2181726

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1053 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0423%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1053	likely benign
REVEL	0.259	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 1.4	GERP 0.72, phastCons 0.001
Regional constraint	o/e 1.03	unconstrained · MANE · 217 bp · p 0.87 · regional, not allelic
Overall
CADD	17.43	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 0.0423% East Asian · 19/44,896 alleles

Filtering AF 0.0276% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.023%

Overall 0.00192% 31/1,614,090 alleles · ultra-rare exomes 26/1,461,892 · genomes 5/152,198 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0423%	2,363
Remaining individualsnot grpmax-eligible	0.0096%	10,415
European (non-Finnish)	0.000508%	196,675

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.Pro278Arg
Coding: c.833C>G
MANE Select: NM_006662
dbSNP: rs759291172
Type: single nucleotide variant
Location: chr16:30709712 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 278: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SRCAP p.Pro278Thr Uncertain significance ★★ ⚠ same residue
SRCAP p.Pro278Ala Uncertain significance ★ ⚠ same residue
SRCAP p.Pro278= Likely benign ★ same residue
SRCAP p.Gln2407Ter Pathogenic ★★ same condition
SRCAP p.Ala1152Val Uncertain significance ★★ ⚠ same condition
SRCAP p.Ala1161Thr Uncertain significance ★★ ⚠ same condition
SRCAP p.Ala1570Thr Uncertain significance ★★ ⚠ same condition
SRCAP p.Ala1584Gly Uncertain significance ★★ same condition

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-pro278arg (accessed [today's date]).

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