Is AMPD1 p.Pro539Ser (c.1615C>T) pathogenic?

AMPD1 p.Pro539Ser (c.1615C>T) is classified Uncertain significance in AMPD1 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.9855); Absent from gnomAD v4.1; Associated with autism.

What condition is associated with AMPD1 p.Pro539Ser (c.1615C>T)?

AMPD1 p.Pro539Ser (c.1615C>T) is associated with autism (ClinVar).

How common is AMPD1 p.Pro539Ser (c.1615C>T) in the general population?

AMPD1 p.Pro539Ser (c.1615C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AMPD1 p.Pro539Ser (c.1615C>T)?

AlphaMissense predicts likely pathogenic (score 0.9855) — an in-silico prediction, not a clinical call.

AMPD1 p.Pro539Ser

c.1615C>T · rs587779372 · VCV91873

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9855 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

autism

Computational evidence

Protein change
AlphaMissense	0.9855	likely pathogenic · top 6% in AMPD1
REVEL	0.936	strongly pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
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 1.00	unconstrained · MANE · 21 kb · p 0.9 · regional, not allelic
Overall
CADD	28.3	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P572S vs ClinVar P539S) — verify the residue.

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: AMPD1
Protein: p.Pro539Ser
Coding: c.1615C>T
MANE Select: NM_000036
dbSNP: rs587779372
Type: single nucleotide variant
Location: chr1:114675594 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.84

Full AMPD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autism — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AMPD1 p.Pro539= Likely benign ★ same residue
AMPD1 p.Arg467Cys Uncertain significance ★★ ⚠ same condition
AMPD1 p.Asp170Val Uncertain significance ★★ ⚠ same condition
AMPD1 p.Asp243Asn Uncertain significance ★★ ⚠ same condition
AMPD1 p.Ile169Met Uncertain significance ★★ ⚠ same condition
AMPD1 c.-30G>A Uncertain significance ★ ⚠ same condition
AMPD1 c.-69C>G Uncertain significance ★ ⚠ same condition
AMPD1 p.Cys450Trp 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/ampd1-p-pro539ser (accessed [today's date]).

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