Is AAMP p.Ser155Arg (c.465T>A) pathogenic?

AAMP p.Ser155Arg (c.465T>A) is classified Uncertain significance in AAMP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-01). AlphaMissense: likely pathogenic (0.9709); Very rare (popmax 0.00167%, amr).

How common is AAMP p.Ser155Arg (c.465T>A) in the general population?

AAMP p.Ser155Arg (c.465T>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about AAMP p.Ser155Arg (c.465T>A)?

AlphaMissense predicts likely pathogenic (score 0.9709) — an in-silico prediction, not a clinical call.

AAMP p.Ser155Arg

c.465T>A · VCV4215039

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9709 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9709	likely pathogenic
REVEL	0.499	indeterminate
SaProt	LLR -13.14	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.034	GERP 1.1, phastCons 0.038
Regional constraint	o/e 0.75	unconstrained · MANE · 5,550 bp · p 3.7e-09 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00167% Admixed American · 1/60,014 alleles

Overall 6.84e-05% 1/1,461,886 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: AAMP
Protein: p.Ser155Arg
Coding: c.465T>A
MANE Select: NM_001087
Type: single nucleotide variant
Location: chr2:218266916 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.55

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

Similar variants

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
AAMP p.Arg352Lys 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-ser155arg (accessed [today's date]).

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