Is SRCAP p.Ser520Asn (c.1559G>A) pathogenic?

SRCAP p.Ser520Asn (c.1559G>A) is classified Benign/Likely benign in SRCAP (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.0778); Low-frequency (popmax 1.44%, mid); Associated with Inborn genetic diseases.

What condition is associated with SRCAP p.Ser520Asn (c.1559G>A)?

SRCAP p.Ser520Asn (c.1559G>A) is associated with Inborn genetic diseases (ClinVar).

How common is SRCAP p.Ser520Asn (c.1559G>A) in the general population?

SRCAP p.Ser520Asn (c.1559G>A) is low-frequency (popmax 1.44%, mid) (gnomAD).

What do computational predictors say about SRCAP p.Ser520Asn (c.1559G>A)?

AlphaMissense predicts likely benign (score 0.0778) — an in-silico prediction, not a clinical call.

SRCAP p.Ser520Asn

c.1559G>A · rs139339184 · VCV218688

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

AlphaMissense

likely benign

0.0778 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.44%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0778	likely benign
REVEL	0.236	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 4.4	GERP 1.5, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 2,095 bp · p 0.41 · regional, not allelic
Overall
CADD	21.1	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 1.44% Middle Eastern · 87/6,060 alleles

Filtering AF 1.19% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1%

Overall 0.0889% 1,435/1,613,902 alleles · low-frequency exomes 1,292/1,461,766 · genomes 143/152,136 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.44%	70
Ashkenazi Jewishnot grpmax-eligible	1.12%	89
Remaining individualsnot grpmax-eligible	0.179%	558
Admixed American	0.17%	588
European (non-Finnish)	0.0636%	1,571
African / African-American	0.0427%	2,344
South Asian	0.0209%	4,793

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.Ser520Asn
Coding: c.1559G>A
MANE Select: NM_006662
dbSNP: rs139339184
Type: single nucleotide variant
Location: chr16:30711901 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 520: a UniProt-annotated variant site (in dehmba); 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.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
SRCAP p.Ala1985Thr Uncertain significance ★★ same condition
SRCAP p.Ala2699Val Uncertain significance ★★ ⚠ same condition
SRCAP p.Ala2945Val 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-ser520asn (accessed [today's date]).

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