Is SRCAP p.Glu408Asp (c.1224G>C) pathogenic?

SRCAP p.Glu408Asp (c.1224G>C) is classified Benign/Likely benign in SRCAP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.0828); Rare (popmax 0.971%, sas); Associated with Inborn genetic diseases.

What condition is associated with SRCAP p.Glu408Asp (c.1224G>C)?

SRCAP p.Glu408Asp (c.1224G>C) is associated with Inborn genetic diseases (ClinVar).

How common is SRCAP p.Glu408Asp (c.1224G>C) in the general population?

SRCAP p.Glu408Asp (c.1224G>C) is rare (popmax 0.971%, sas) (gnomAD).

What do computational predictors say about SRCAP p.Glu408Asp (c.1224G>C)?

AlphaMissense predicts likely benign (score 0.0828) — an in-silico prediction, not a clinical call.

SRCAP p.Glu408Asp

c.1224G>C · rs557790573 · VCV788147

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0828 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.971%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0828	likely benign
REVEL	0.232	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.5	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 2,095 bp · p 0.41 · regional, not allelic
Overall
CADD	14.98	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 0.971% South Asian · 884/91,080 alleles

Filtering AF 0.917% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.896%

Overall 0.0587% 947/1,614,182 alleles · rare exomes 891/1,461,844 · genomes 56/152,338 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.971%	103
Remaining individualsnot grpmax-eligible	0.064%	1,563
Middle Eastern	0.033%	3,030
African / African-American	0.00266%	37,525
European (non-Finnish)	0.00161%	62,107

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.Glu408Asp
Coding: c.1224G>C
MANE Select: NM_006662
dbSNP: rs557790573
Type: single nucleotide variant
Location: chr16:30710843 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 408: 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-glu408asp (accessed [today's date]).

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