Is MCM3AP p.Ala487Val (c.1460C>T) pathogenic?

MCM3AP p.Ala487Val (c.1460C>T) is classified Uncertain significance in MCM3AP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely pathogenic (0.6949); Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MCM3AP p.Ala487Val (c.1460C>T)?

MCM3AP p.Ala487Val (c.1460C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MCM3AP p.Ala487Val (c.1460C>T) in the general population?

MCM3AP p.Ala487Val (c.1460C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about MCM3AP p.Ala487Val (c.1460C>T)?

AlphaMissense predicts likely pathogenic (score 0.6949) — an in-silico prediction, not a clinical call.

MCM3AP p.Ala487Val

c.1460C>T · VCV4105141

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6949 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6949	likely pathogenic
REVEL	0.304	indeterminate
SaProt	LLR -9.51	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 7,693 bp · p 0.002 · regional, not allelic
Overall
CADD	28.3	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 8.48e-05% European (non-Finnish) · 1/1,178,838 alleles

Overall 6.2e-05% 1/1,612,460 alleles · very rare exomes 1/1,460,146 · genomes 0/152,314 · 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: MCM3AP
Protein: p.Ala487Val
Coding: c.1460C>T
MANE Select: NM_003906
Type: single nucleotide variant
Location: chr21:46280559 (GRCh38)
Gene constraint: LOEUF 0.769 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.83 · 7 PDB

Full MCM3AP 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

MCM3AP p.Ala487= Likely benign ★ same residue
MCM3AP p.Ala1102Ser Uncertain significance ★★ ⚠ same condition
MCM3AP p.Ala1117Val Uncertain significance ★★ ⚠ same condition
MCM3AP p.Ala1283Thr Uncertain significance ★★ ⚠ same condition
MCM3AP p.Ala172Ser Uncertain significance ★★ ⚠ same condition
MCM3AP p.Ala17Gly Uncertain significance ★★ ⚠ same condition
MCM3AP p.Ala277Pro Uncertain significance ★★ ⚠ same condition
MCM3AP p.Ala499Thr 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/mcm3ap-p-ala487val (accessed [today's date]).

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