Is AMPD3 p.Ala186Val (c.557C>T) pathogenic?

AMPD3 p.Ala186Val (c.557C>T) is classified Uncertain significance in AMPD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-09). AlphaMissense: likely benign (0.0689); Ultra-rare (popmax 0.036%, mid).

How common is AMPD3 p.Ala186Val (c.557C>T) in the general population?

AMPD3 p.Ala186Val (c.557C>T) is ultra-rare (popmax 0.036%, mid) (gnomAD).

What do computational predictors say about AMPD3 p.Ala186Val (c.557C>T)?

AlphaMissense predicts likely benign (score 0.0689) — an in-silico prediction, not a clinical call.

AMPD3 p.Ala186Val

c.557C>T · rs202051288 · VCV2238271

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0689 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.036%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0689	likely benign
REVEL	0.005	strongly benign-leaning
SaProt	LLR -6.89	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 -0.57	GERP -0.35
Regional constraint	o/e 0.87	unconstrained · MANE · 44 kb · p 2.4e-05 · regional, not allelic
Overall
CADD	4.885	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

Grpmax group 0.036% Middle Eastern · 2/5,554 alleles

Filtering AF 0.0234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00638% 103/1,613,180 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.036%	2,777
Admixed American	0.035%	2,858
East Asian	0.00891%	11,221
Remaining individualsnot grpmax-eligible	0.00641%	15,608
European (non-Finnish)	0.00576%	17,351
African / African-American	0.004%	25,018
Finnishnot grpmax-eligible	0.00157%	63,832

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: AMPD3
Protein: p.Ala186Val
Coding: c.557C>T
MANE Select: NM_001025389
dbSNP: rs202051288
Type: single nucleotide variant
Location: chr11:10482193 (GRCh38)
Gene constraint: LOEUF 0.817 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.74
Residue 186: the 'disordered' region

Full AMPD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AMPD3 p.Ala186Glu Uncertain significance ★ ⚠ same residue
AMPD3 c.1135-5C>A Uncertain significance ★★ same type
AMPD3 c.1135-6C>G Uncertain significance ★★ same type
AMPD3 c.1267-3C>T Uncertain significance ★★ same type
AMPD3 c.*287T>C Uncertain significance ★★ same type
AMPD3 c.*75C>T Uncertain significance ★★ same type
AMPD3 p.Ala141= Uncertain significance ★★ same type
AMPD3 p.Arg426Trp 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/ampd3-p-ala186val (accessed [today's date]).

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