Is NT5C3A p.Phe31= (c.93C>T) pathogenic?

NT5C3A p.Phe31= (c.93C>T) is classified Likely benign in NT5C3A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-29). Very rare (popmax 0.00134%, afr); Associated with hemolytic anemia due to pyrimidine 5' nucleotidase deficiency.

What condition is associated with NT5C3A p.Phe31= (c.93C>T)?

NT5C3A p.Phe31= (c.93C>T) is associated with hemolytic anemia due to pyrimidine 5' nucleotidase deficiency (ClinVar).

How common is NT5C3A p.Phe31= (c.93C>T) in the general population?

NT5C3A p.Phe31= (c.93C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

NT5C3A p.Phe31=

Q: How is Hemolytic anemia due to pyrimidine 5' nucleotidase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.93C>T · VCV3766853

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

hemolytic anemia due to pyrimidine 5' nucleotidase 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 3.5	GERP 1.6, phastCons 1
Overall
CADD	15.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,702 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,609,216 alleles · very rare exomes 0/1,457,036 · genomes 3/152,180 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,702
European (non-Finnish)	0.00017%	589,317

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: NT5C3A
Protein: p.Phe31=
Coding: c.93C>T
MANE Select: NM_001002010
Type: single nucleotide variant
Location: chr7:33062613 (GRCh38)
Gene constraint: LOEUF 1.137 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.29 · 3 PDB

Full NT5C3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hemolytic anemia due to pyrimidine 5' nucleotidase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hemolytic anemia due to pyrimidine 5' nucleotidase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

NT5C3A p.Phe31Leu Benign/Likely benign ★★ same residue
POMP p.Leu31Phe Uncertain significance ★★ ⚠ same residue
NT5C3A p.Asp132Val Pathogenic/Likely pathogenic ★★ same condition
NT5C3A p.Asn259Ser Uncertain significance ★★ same condition
NT5C3A p.Asp185Gly Uncertain significance ★★ same condition
NT5C3A p.Glu301Asp Uncertain significance ★★ same condition
NT5C3A p.Leu270Pro Uncertain significance ★★ same condition
NT5C3A p.Lys109Gln 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/nt5c3a-p-phe31 (accessed [today's date]).

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