Is AMPD3 p.His377= (c.1131C>T) pathogenic?

AMPD3 p.His377= (c.1131C>T) is classified Benign/Likely benign in AMPD3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2021-08-06). Low-frequency (popmax 3.27%, afr); Associated with Erythrocyte AMP deaminase deficiency.

What condition is associated with AMPD3 p.His377= (c.1131C>T)?

AMPD3 p.His377= (c.1131C>T) is associated with Erythrocyte AMP deaminase deficiency (ClinVar).

How common is AMPD3 p.His377= (c.1131C>T) in the general population?

AMPD3 p.His377= (c.1131C>T) is low-frequency (popmax 3.27%, afr) (gnomAD).

AMPD3 p.His377=

c.1131C>T · rs76407515 · VCV302166

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.27%, afr)

Conditions

Erythrocyte AMP deaminase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.8
Overall
CADD	0.232	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.27% African / African-American · 2,456/75,048 alleles

Filtering AF 3.16% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.12%

Overall 0.182% 2,936/1,613,854 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.27%	31
Remaining individualsnot grpmax-eligible	0.325%	308
Admixed American	0.273%	366
Middle Eastern	0.248%	404
South Asian	0.00878%	11,385
European (non-Finnish)	0.00754%	13,257
Finnishnot grpmax-eligible	0.00156%	63,924

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.His377=
Coding: c.1131C>T
MANE Select: NM_001025389
dbSNP: rs76407515
Type: single nucleotide variant
Location: chr11:10493540 (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 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
AMPD3 p.Arg576= 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-his377 (accessed [today's date]).

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