Is SRCAP p.Asn473Asp (c.1417A>G) pathogenic?

SRCAP p.Asn473Asp (c.1417A>G) is classified Conflicting classifications of pathogenicity in SRCAP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-08-30). AlphaMissense: likely benign (0.0659); Ultra-rare (popmax 0.0582%, sas); Associated with Inborn genetic diseases.

What condition is associated with SRCAP p.Asn473Asp (c.1417A>G)?

SRCAP p.Asn473Asp (c.1417A>G) is associated with Inborn genetic diseases (ClinVar).

How common is SRCAP p.Asn473Asp (c.1417A>G) in the general population?

SRCAP p.Asn473Asp (c.1417A>G) is ultra-rare (popmax 0.0582%, sas) (gnomAD).

What do computational predictors say about SRCAP p.Asn473Asp (c.1417A>G)?

AlphaMissense predicts likely benign (score 0.0659) — an in-silico prediction, not a clinical call.

SRCAP p.Asn473Asp

c.1417A>G · VCV4174642

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0659 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0582%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0659	likely benign
REVEL	0.168	moderately 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 1.1	GERP -0.45, phastCons 0.005
Regional constraint	o/e 0.95	unconstrained · MANE · 2,095 bp · p 0.41 · regional, not allelic
Overall
CADD	12.57	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 0.0582% South Asian · 53/91,084 alleles

Filtering AF 0.0457% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0412%

Overall 0.00409% 66/1,614,108 alleles · ultra-rare exomes 61/1,461,858 · genomes 5/152,250 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0582%	1,719
Remaining individualsnot grpmax-eligible	0.0064%	15,626
East Asian	0.00446%	22,435
African / African-American	0.004%	25,009
Admixed American	0.00167%	59,998
European (non-Finnish)	0.000254%	393,340

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.Asn473Asp
Coding: c.1417A>G
MANE Select: NM_006662
Type: single nucleotide variant
Location: chr16:30711669 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 473: 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.Asn473Ser 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
SRCAP p.Ala2699Val 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-asn473asp (accessed [today's date]).

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