Is SRCAP p.Ser1844Cys (c.5531C>G) pathogenic?

SRCAP p.Ser1844Cys (c.5531C>G) is classified Benign/Likely benign in SRCAP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-08). AlphaMissense: likely benign (0.0856); Rare (popmax 0.509%, afr); Associated with Inborn genetic diseases.

What condition is associated with SRCAP p.Ser1844Cys (c.5531C>G)?

SRCAP p.Ser1844Cys (c.5531C>G) is associated with Inborn genetic diseases (ClinVar).

How common is SRCAP p.Ser1844Cys (c.5531C>G) in the general population?

SRCAP p.Ser1844Cys (c.5531C>G) is rare (popmax 0.509%, afr) (gnomAD).

What do computational predictors say about SRCAP p.Ser1844Cys (c.5531C>G)?

AlphaMissense predicts likely benign (score 0.0856) — an in-silico prediction, not a clinical call.

SRCAP p.Ser1844Cys

c.5531C>G · rs78037619 · VCV195886

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0856 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.509%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0856	likely benign
REVEL	0.147	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.2	GERP 0.64, phastCons 0.61
Regional constraint	o/e 1.03	unconstrained · MANE · 8,776 bp · p 0.24 · regional, not allelic
Overall
CADD	18.12	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 0.509% African / African-American · 382/75,052 alleles

Filtering AF 0.467% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.45%

Overall 0.0263% 425/1,614,218 alleles · rare exomes 192/1,461,892 · genomes 233/152,326 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.509%	196
Remaining individualsnot grpmax-eligible	0.032%	3,125
Admixed American	0.0317%	3,159
Middle Eastern	0.0165%	6,062
South Asian	0.00329%	30,361

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.Ser1844Cys
Coding: c.5531C>G
MANE Select: NM_006662
dbSNP: rs78037619
Type: single nucleotide variant
Location: chr16:30724955 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1844: 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

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

Similar variants

SRCAP p.Ser1844Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
SRCAP p.Ser1844Pro Uncertain significance ★ ⚠ 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
SRCAP p.Ala1985Thr 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-ser1844cys (accessed [today's date]).

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