Is SMARCD2 p.Pro242Arg (c.725C>G) pathogenic?

SMARCD2 p.Pro242Arg (c.725C>G) is classified Uncertain significance in SMARCD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-13). AlphaMissense: ambiguous (0.5634); Very rare (popmax 8.52e-05%, nfe).

How common is SMARCD2 p.Pro242Arg (c.725C>G) in the general population?

SMARCD2 p.Pro242Arg (c.725C>G) is very rare (popmax 8.52e-05%, nfe) (gnomAD).

What do computational predictors say about SMARCD2 p.Pro242Arg (c.725C>G)?

AlphaMissense predicts ambiguous (score 0.5634) — an in-silico prediction, not a clinical call.

SMARCD2 p.Pro242Arg

c.725C>G · VCV3674371

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5634 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.52e-05%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5634	ambiguous
REVEL	0.158	moderately benign-leaning
SaProt	LLR -10.58	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	Δ0.30	acceptor gain · deltas
Pangolin	Δ0.34	gain · loss 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	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	29.2	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 8.52e-05% European (non-Finnish) · 1/1,173,536 alleles

Overall 6.22e-05% 1/1,607,000 alleles · very rare exomes 1/1,454,692 · genomes 0/152,308 · joint denominator

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.Pro242Arg
Coding: c.725C>G
MANE Select: NM_001098426
Type: single nucleotide variant
Location: chr17:63834799 (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

Similar variants

SMARCD2 p.Pro242Thr Uncertain significance ★ ⚠ same residue
SMARCD2 p.Pro242= Likely benign ★ same residue
SMARCD2 p.Arg192Ter Pathogenic/Likely pathogenic ★★ same type
SMARCD2 c.922-3C>T Uncertain significance ★★ same type
SMARCD2 p.Ala434Thr Uncertain significance ★★ ⚠ same type
SMARCD2 p.Ala6Val Uncertain significance ★★ ⚠ same type
SMARCD2 p.Arg118Cys Uncertain significance ★★ ⚠ same type
SMARCD2 p.Arg148Gln Uncertain significance ★★ ⚠ same type

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-pro242arg (accessed [today's date]).

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