Is MCCC1 p.Pro28Ser (c.82C>T) pathogenic?

MCCC1 p.Pro28Ser (c.82C>T) is classified Uncertain significance in MCCC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-18). AlphaMissense: likely benign (0.0807); Very rare (popmax 0.00255%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MCCC1 p.Pro28Ser (c.82C>T)?

MCCC1 p.Pro28Ser (c.82C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MCCC1 p.Pro28Ser (c.82C>T) in the general population?

MCCC1 p.Pro28Ser (c.82C>T) is very rare (popmax 0.00255%, nfe) (gnomAD).

What do computational predictors say about MCCC1 p.Pro28Ser (c.82C>T)?

AlphaMissense predicts likely benign (score 0.0807) — an in-silico prediction, not a clinical call.

MCCC1 p.Pro28Ser

c.82C>T · VCV3544071

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0807 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00255%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0807	likely benign
REVEL	0.4	indeterminate
SaProt	LLR -5.98	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 0.51, phastCons 0.87
Regional constraint	o/e 0.89	unconstrained · MANE · 84 kb · p 0.0012 · regional, not allelic
Overall
CADD	14.9	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

Grpmax group 0.00255% European (non-Finnish) · 30/1,175,310 alleles

Filtering AF 0.00181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00157%

Overall 0.00188% 30/1,599,538 alleles · very rare

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: MCCC1
Protein: p.Pro28Ser
Coding: c.82C>T
MANE Select: NM_020166
Type: single nucleotide variant
Location: chr3:183099359 (GRCh38)
Gene constraint: LOEUF 0.819 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.53 · 14 PDB

Full MCCC1 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

MCCC1 p.Pro28Leu Uncertain significance ★ ⚠ same residue
MCCC1 p.Pro28= Likely benign ★ same residue
MCCC1 p.Ala101Thr Uncertain significance ★★ ⚠ same condition
MCCC1 p.Ala291= Uncertain significance ★★ same condition
MCCC1 p.Ala530Gly Uncertain significance ★★ ⚠ same condition
MCCC1 p.Arg281Gln Uncertain significance ★★ ⚠ same condition
MCCC1 p.Arg409Leu Uncertain significance ★★ ⚠ same condition
MCCC1 p.Asn267Lys 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/mccc1-p-pro28ser (accessed [today's date]).

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