Is SRCAP p.Arg2329Gln (c.6986G>A) pathogenic?

SRCAP p.Arg2329Gln (c.6986G>A) is classified Likely benign in SRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2020-04-27). AlphaMissense: likely benign (0.1901); Very rare (popmax 0.00263%, nfe); Associated with intellectual disability.

What condition is associated with SRCAP p.Arg2329Gln (c.6986G>A)?

SRCAP p.Arg2329Gln (c.6986G>A) is associated with intellectual disability (ClinVar).

How common is SRCAP p.Arg2329Gln (c.6986G>A) in the general population?

SRCAP p.Arg2329Gln (c.6986G>A) is very rare (popmax 0.00263%, nfe) (gnomAD).

What do computational predictors say about SRCAP p.Arg2329Gln (c.6986G>A)?

AlphaMissense predicts likely benign (score 0.1901) — an in-silico prediction, not a clinical call.

SRCAP p.Arg2329Gln

c.6986G>A · VCV4075304

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1901 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00263%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.1901	likely benign
REVEL	0.263	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 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 918 bp · p 1.2e-06 · regional, not allelic
Overall
CADD	27.0	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 0.00263% European (non-Finnish) · 31/1,180,030 alleles

Filtering AF 0.00188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00164%

Overall 0.00198% 32/1,614,096 alleles · very rare exomes 30/1,461,888 · genomes 2/152,208 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00263%	38,066
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Arg2329Gln
Coding: c.6986G>A
MANE Select: NM_006662
Type: single nucleotide variant
Location: chr16:30736602 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2329: the 'disordered' region; a UniProt-annotated variant site (in dehmba)

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

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SRCAP p.Arg2329Ter Pathogenic/Likely pathogenic ★★ same residue
SRCAP p.Arg2329Leu Uncertain significance ★★ same residue
SRCAP p.Arg2151His Uncertain significance ★ ⚠ same condition
SRCAP p.Thr1690Ala Conflicting classifications of pathogenicity ★ ⚠ same condition
SRCAP p.Val1795Ile Uncertain significance ★ ⚠ same condition
SRCAP p.Pro1762Gln Uncertain significance ⚠ same condition
SRCAP p.Arg2435Ter Pathogenic/Likely pathogenic ★★ same type
SRCAP p.Arg2444Ter 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-arg2329gln (accessed [today's date]).

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