Is SGCA p.Arg156Ser (c.466C>A) pathogenic?

SGCA p.Arg156Ser (c.466C>A) is classified Uncertain significance in SGCA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-02-15). AlphaMissense: likely benign (0.161); No allele count reported in gnomAD v4.1 (AN 1,587,094); Associated with Inborn genetic diseases.

What condition is associated with SGCA p.Arg156Ser (c.466C>A)?

SGCA p.Arg156Ser (c.466C>A) is associated with Inborn genetic diseases, autosomal recessive limb-girdle muscular dystrophy type 2D (ClinVar).

How common is SGCA p.Arg156Ser (c.466C>A) in the general population?

SGCA p.Arg156Ser (c.466C>A) is no allele count reported in gnomAD v4.1 (AN 1,587,094) (gnomAD).

What do computational predictors say about SGCA p.Arg156Ser (c.466C>A)?

AlphaMissense predicts likely benign (score 0.161) — an in-silico prediction, not a clinical call.

SGCA p.Arg156Ser

c.466C>A · rs538696245 · VCV2379719

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.161 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,587,094)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.161	likely benign
REVEL	0.45	indeterminate
SaProt	LLR -5.58	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 1.4, phastCons 0.99
Regional constraint	o/e 0.91	unconstrained · MANE · 9,393 bp · p 0.033 · regional, not allelic
Overall
CADD	19.71	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,587,094). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SGCA
Protein: p.Arg156Ser
Coding: c.466C>A
MANE Select: NM_000023
dbSNP: rs538696245
Type: single nucleotide variant
Location: chr17:50168454 (GRCh38)
Gene constraint: LOEUF 1.273 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.15

Full SGCA 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

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2D

Similar variants

SGCA p.Arg156Cys Uncertain significance ★★ ⚠ same residue
SGCA p.Arg156His Uncertain significance ★★ ⚠ same residue
SGCA p.Arg156= Likely benign ★ same residue
SGCA c.37+6T>C Pathogenic ★★★ same condition
SGCA c.585-1G>A Pathogenic ★★★ same condition
SGCA c.957-11C>G Likely pathogenic ★★★ same condition
SGCA p.Ala107Val Likely pathogenic ★★★ ⚠ same condition
SGCA p.Arg192Ter Pathogenic ★★★ 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/sgca-p-arg156ser (accessed [today's date]).

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