Is SRCAP p.Arg2017Gln (c.6050G>A) pathogenic?

SRCAP p.Arg2017Gln (c.6050G>A) is classified Conflicting classifications of pathogenicity in SRCAP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-11-11). AlphaMissense: likely benign (0.1715); Ultra-rare (popmax 0.0329%, mid); Associated with Floating-Harbor syndrome.

What condition is associated with SRCAP p.Arg2017Gln (c.6050G>A)?

SRCAP p.Arg2017Gln (c.6050G>A) is associated with Floating-Harbor syndrome, developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (ClinVar).

How common is SRCAP p.Arg2017Gln (c.6050G>A) in the general population?

SRCAP p.Arg2017Gln (c.6050G>A) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about SRCAP p.Arg2017Gln (c.6050G>A)?

AlphaMissense predicts likely benign (score 0.1715) — an in-silico prediction, not a clinical call.

SRCAP p.Arg2017Gln

c.6050G>A · rs754274438 · VCV1501185

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1715 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Conditions

Floating-Harbor syndrome

Computational evidence

Protein change
AlphaMissense	0.1715	likely benign
REVEL	0.31	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 8,776 bp · p 0.24 · regional, not allelic
Overall
CADD	23.2	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 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.00273% 44/1,614,022 alleles · ultra-rare exomes 42/1,461,894 · genomes 2/152,128 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
European (non-Finnish)	0.00322%	31,053
South Asian	0.0022%	45,543
Admixed American	0.00167%	59,984
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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.Arg2017Gln
Coding: c.6050G>A
MANE Select: NM_006662
dbSNP: rs754274438
Type: single nucleotide variant
Location: chr16:30729495 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2017: an α-helix; a UniProt-annotated variant site (in dehmba)

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

Disease context

Floating-Harbor syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities

Similar variants

SRCAP p.Arg2017Trp Uncertain significance ★★ same residue
SRCAP p.Arg2017Pro Uncertain significance ★ same residue
SRCAP p.Arg2329Ter Pathogenic/Likely pathogenic ★★ same condition
SRCAP p.Arg2435Ter Pathogenic/Likely pathogenic ★★ same condition
SRCAP p.Arg2444Ter Pathogenic ★★ same condition
SRCAP p.Arg2718Ter Pathogenic/Likely pathogenic ★★ same condition
SRCAP p.Arg2748Ter Pathogenic ★★ same condition
SRCAP p.Gln2407Ter Pathogenic ★★ 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-arg2017gln (accessed [today's date]).

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