Is MCM3 p.Ser86Phe (c.257C>T) pathogenic?

MCM3 p.Ser86Phe (c.257C>T) is classified Uncertain significance in MCM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-20). AlphaMissense: likely pathogenic (0.7404); Very rare (popmax 6.2e-05%).

How common is MCM3 p.Ser86Phe (c.257C>T) in the general population?

MCM3 p.Ser86Phe (c.257C>T) is very rare (popmax 6.2e-05%) (gnomAD).

What do computational predictors say about MCM3 p.Ser86Phe (c.257C>T)?

AlphaMissense predicts likely pathogenic (score 0.7404) — an in-silico prediction, not a clinical call.

MCM3 p.Ser86Phe

c.257C>T · VCV3293657

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7404 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7404	likely pathogenic
REVEL	0.271	benign-leaning
SaProt	LLR -8.34	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 7,062 bp · p 0.93 · regional, not allelic
Overall
CADD	29.6	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 6.2e-05%

Overall 6.2e-05% 1/1,614,030 alleles · very rare exomes 1/1,461,882 · genomes 0/152,148 · 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: MCM3
Protein: p.Ser86Phe
Coding: c.257C>T
MANE Select: NM_002388
Type: single nucleotide variant
Location: chr6:52282796 (GRCh38)
Gene constraint: LOEUF 0.812 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.04 · 29 PDB
Residue 86: an α-helix

Full MCM3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MCM3 p.Ala262Ser Uncertain significance ★ ⚠ same type
MCM3 p.Ala278Thr Uncertain significance ★ ⚠ same type
MCM3 p.Ala300Gly Uncertain significance ★ ⚠ same type
MCM3 p.Ala509Val Uncertain significance ★ ⚠ same type
MCM3 p.Ala528Gly Uncertain significance ★ ⚠ same type
MCM3 p.Ala608Thr Uncertain significance ★ ⚠ same type
MCM3 p.Arg114Trp Uncertain significance ★ ⚠ same type
MCM3 p.Arg138Cys 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/mcm3-p-ser86phe (accessed [today's date]).

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