Is MCCC2 p.Ser328Arg (c.984C>A) pathogenic?

MCCC2 p.Ser328Arg (c.984C>A) is classified Uncertain significance in MCCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-19). AlphaMissense: ambiguous (0.54); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MCCC2 p.Ser328Arg (c.984C>A)?

MCCC2 p.Ser328Arg (c.984C>A) is associated with Inborn genetic diseases (ClinVar).

How common is MCCC2 p.Ser328Arg (c.984C>A) in the general population?

MCCC2 p.Ser328Arg (c.984C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MCCC2 p.Ser328Arg (c.984C>A)?

AlphaMissense predicts ambiguous (score 0.54) — an in-silico prediction, not a clinical call.

MCCC2 p.Ser328Arg

c.984C>A · rs2530829405 · VCV2336913

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.54 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.54	ambiguous
REVEL	0.389	indeterminate
SaProt	LLR -9.80	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.29	GERP -0.087
Regional constraint	o/e 0.97	unconstrained · MANE · 69 kb · p 0.42 · regional, not allelic
Overall
CADD	14.41	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MCCC2
Protein: p.Ser328Arg
Coding: c.984C>A
MANE Select: NM_022132
dbSNP: rs2530829405
Type: single nucleotide variant
Location: chr5:71635231 (GRCh38)
Gene constraint: LOEUF 0.832 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.82 · 14 PDB
Residue 328: the coa carboxyltransferase c-terminal domain; the 'carboxyltransferase' region

Full MCCC2 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

MCCC2 p.Ser328Gly Uncertain significance ★ ⚠ same residue
MCCC2 p.Ser328Asn Uncertain significance ⚠ same residue
MCCC2 c.281+4C>T Uncertain significance ★★ same condition
MCCC2 p.Ala428Thr Uncertain significance ★★ ⚠ same condition
MCCC2 p.Ala551Thr Uncertain significance ★★ ⚠ same condition
MCCC2 p.Arg234His Uncertain significance ★★ ⚠ same condition
MCCC2 p.Asn205Lys Uncertain significance ★★ ⚠ same condition
MCCC2 p.Asn480Asp 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/mccc2-p-ser328arg (accessed [today's date]).

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