Is AMPD3 p.Asn279Ser (c.836A>G) pathogenic?

AMPD3 p.Asn279Ser (c.836A>G) is classified Uncertain significance in AMPD3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-05-26). AlphaMissense: likely benign (0.0815); Rare (popmax 0.221%, nfe); Associated with Erythrocyte AMP deaminase deficiency.

What condition is associated with AMPD3 p.Asn279Ser (c.836A>G)?

AMPD3 p.Asn279Ser (c.836A>G) is associated with Erythrocyte AMP deaminase deficiency (ClinVar).

How common is AMPD3 p.Asn279Ser (c.836A>G) in the general population?

AMPD3 p.Asn279Ser (c.836A>G) is rare (popmax 0.221%, nfe) (gnomAD).

What do computational predictors say about AMPD3 p.Asn279Ser (c.836A>G)?

AlphaMissense predicts likely benign (score 0.0815) — an in-silico prediction, not a clinical call.

AMPD3 p.Asn279Ser

c.836A>G · rs144613367 · VCV879016

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0815 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.221%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Erythrocyte AMP deaminase deficiency

Computational evidence

Protein change
AlphaMissense	0.0815	likely benign
REVEL	0.437	indeterminate
SaProt	LLR -5.60	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 44 kb · p 2.4e-05 · regional, not allelic
Overall
CADD	23.3	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 0.221% European (non-Finnish) · 2,609/1,180,014 alleles

Filtering AF 0.214% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.211%

Overall 0.178% 2,880/1,614,136 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.221%	452
Ashkenazi Jewishnot grpmax-eligible	0.162%	617
Remaining individualsnot grpmax-eligible	0.126%	791
South Asian	0.0867%	1,153
Finnishnot grpmax-eligible	0.0406%	2,462
African / African-American	0.0333%	3,001
Middle Eastern	0.033%	3,031
Admixed American	0.02%	5,002

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.Asn279Ser
Coding: c.836A>G
MANE Select: NM_001025389
dbSNP: rs144613367
Type: single nucleotide variant
Location: chr11:10487261 (GRCh38)
Gene constraint: LOEUF 0.817 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.74

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

Disease context

Erythrocyte AMP deaminase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AMPD3 p.Asn279Lys Uncertain significance ★ ⚠ same residue
AMPD3 c.1135-5C>A Uncertain significance ★★ same condition
AMPD3 c.1135-6C>G Uncertain significance ★★ same condition
AMPD3 c.1267-3C>T Uncertain significance ★★ same condition
AMPD3 c.*287T>C Uncertain significance ★★ same condition
AMPD3 c.*75C>T Uncertain significance ★★ same condition
AMPD3 p.Ala141= Uncertain significance ★★ same condition
AMPD3 p.Arg426Trp 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/ampd3-p-asn279ser (accessed [today's date]).

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