Is MCCC1 p.Ser507Phe (c.1520C>T) pathogenic?

MCCC1 p.Ser507Phe (c.1520C>T) is classified Likely benign in MCCC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-28). AlphaMissense: likely benign (0.1075); Very rare (popmax 0.000508%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MCCC1 p.Ser507Phe (c.1520C>T)?

MCCC1 p.Ser507Phe (c.1520C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MCCC1 p.Ser507Phe (c.1520C>T) in the general population?

MCCC1 p.Ser507Phe (c.1520C>T) is very rare (popmax 0.000508%, nfe) (gnomAD).

What do computational predictors say about MCCC1 p.Ser507Phe (c.1520C>T)?

AlphaMissense predicts likely benign (score 0.1075) — an in-silico prediction, not a clinical call.

MCCC1 p.Ser507Phe

c.1520C>T · VCV4624487

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1075 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1075	likely benign
REVEL	0.448	indeterminate
SaProt	LLR -6.28	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 0.16	GERP -4.3
Regional constraint	o/e 0.89	unconstrained · MANE · 84 kb · p 0.0012 · regional, not allelic
Overall
CADD	4.911	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 0.000508% European (non-Finnish) · 6/1,180,054 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,614,040 alleles · very rare exomes 4/1,461,882 · genomes 2/152,158 · 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: MCCC1
Protein: p.Ser507Phe
Coding: c.1520C>T
MANE Select: NM_020166
Type: single nucleotide variant
Location: chr3:183037292 (GRCh38)
Gene constraint: LOEUF 0.819 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.53 · 14 PDB
Residue 507: an α-helix

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.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
MCCC1 p.Asn603Ser Uncertain significance ★★ ⚠ same condition
MCCC1 p.Asp672Gly 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-ser507phe (accessed [today's date]).

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