Is SMARCD2 p.Asp113Ala (c.338A>C) pathogenic?

SMARCD2 p.Asp113Ala (c.338A>C) is classified Uncertain significance in SMARCD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-25). AlphaMissense: likely pathogenic (0.8065); Very rare (popmax 0.00452%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SMARCD2 p.Asp113Ala (c.338A>C)?

SMARCD2 p.Asp113Ala (c.338A>C) is associated with Inborn genetic diseases (ClinVar).

How common is SMARCD2 p.Asp113Ala (c.338A>C) in the general population?

SMARCD2 p.Asp113Ala (c.338A>C) is very rare (popmax 0.00452%, nfe) (gnomAD).

What do computational predictors say about SMARCD2 p.Asp113Ala (c.338A>C)?

AlphaMissense predicts likely pathogenic (score 0.8065) — an in-silico prediction, not a clinical call.

SMARCD2 p.Asp113Ala

c.338A>C · rs762396735 · VCV2202828

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8065 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00452%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8065	likely pathogenic
REVEL	0.091	moderately benign-leaning
SaProt	LLR -8.33	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 9,733 bp · p 8.5e-11 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00452% European (non-Finnish) · 53/1,172,284 alleles

Filtering AF 0.00353% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0032%

Overall 0.0035% 56/1,601,454 alleles · very rare exomes 53/1,449,302 · genomes 3/152,152 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00452%	22,119
Remaining individualsnot grpmax-eligible	0.00323%	30,936
African / African-American	0.00134%	74,660

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: SMARCD2
Protein: p.Asp113Ala
Coding: c.338A>C
MANE Select: NM_001098426
dbSNP: rs762396735
Type: single nucleotide variant
Location: chr17:63837504 (GRCh38)
Gene constraint: LOEUF 0.762 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.38

Full SMARCD2 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

SMARCD2 p.Ala434Thr Uncertain significance ★★ ⚠ same condition
SMARCD2 p.Arg118Cys Uncertain significance ★★ ⚠ same condition
SMARCD2 p.Arg148Gln Uncertain significance ★★ ⚠ same condition
SMARCD2 p.Arg175His Uncertain significance ★★ ⚠ same condition
SMARCD2 p.Arg360Cys Uncertain significance ★★ ⚠ same condition
SMARCD2 p.Arg473Leu Uncertain significance ★★ ⚠ same condition
SMARCD2 p.Arg476Cys Uncertain significance ★★ ⚠ same condition
SMARCD2 p.Arg494Gln 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/smarcd2-p-asp113ala (accessed [today's date]).

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