Is AAMP p.Pro38Ser (c.112C>T) pathogenic?

AAMP p.Pro38Ser (c.112C>T) is classified Uncertain significance in AAMP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: likely benign (0.0767); Absent from gnomAD v4.1.

How common is AAMP p.Pro38Ser (c.112C>T) in the general population?

AAMP p.Pro38Ser (c.112C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AAMP p.Pro38Ser (c.112C>T)?

AlphaMissense predicts likely benign (score 0.0767) — an in-silico prediction, not a clinical call.

AAMP p.Pro38Ser

c.112C>T · VCV4215063

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0767 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0767	likely benign
REVEL	0.176	moderately benign-leaning
SaProt	LLR -6.30	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 5,550 bp · p 3.7e-09 · regional, not allelic
Overall
CADD	23.5	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

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: AAMP
Protein: p.Pro38Ser
Coding: c.112C>T
MANE Select: NM_001087
Type: single nucleotide variant
Location: chr2:218269975 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.55
Residue 38: the 'disordered' region

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

Similar variants

AAMP p.Pro38Leu Uncertain significance ★ ⚠ same residue
AAMP p.Ala116Gly Uncertain significance ★ ⚠ same type
AAMP p.Ala289Val Uncertain significance ★ ⚠ same type
AAMP p.Ala304Val Uncertain significance ★ ⚠ same type
AAMP p.Ala424Val Uncertain significance ★ ⚠ same type
AAMP p.Arg120Trp Uncertain significance ★ ⚠ same type
AAMP p.Arg222Gln Uncertain significance ★ ⚠ same type
AAMP p.Arg352Gly 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/aamp-p-pro38ser (accessed [today's date]).

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