Is HAX1 p.Phe7= (c.21C>T) pathogenic?

HAX1 p.Phe7= (c.21C>T) is classified Likely benign in HAX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-05). Absent from gnomAD v4.1; Associated with Kostmann syndrome.

What condition is associated with HAX1 p.Phe7= (c.21C>T)?

HAX1 p.Phe7= (c.21C>T) is associated with Kostmann syndrome (ClinVar).

How common is HAX1 p.Phe7= (c.21C>T) in the general population?

HAX1 p.Phe7= (c.21C>T) is absent from gnomAD v4.1 (gnomAD).

How is Kostmann syndrome inherited?

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

HAX1 p.Phe7=

c.21C>T · rs2149138533 · VCV1092301

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Kostmann syndrome

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 -0.37	phastCons 0.13
Overall
CADD	15.27	PHRED · no single calibrated threshold — expert panels disagree

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: HAX1
Protein: p.Phe7=
Coding: c.21C>T
MANE Select: NM_006118
dbSNP: rs2149138533
Type: single nucleotide variant
Location: chr1:154272744 (GRCh38)
Gene constraint: LOEUF 1.132 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.06
Residue 7: the 'required for localization in mitochondria' region

Full HAX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For Kostmann syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

HAX1 c.317-2A>G Likely pathogenic ★★ same condition
HAX1 c.556+1G>A Likely pathogenic ★★ same condition
HAX1 c.556+1G>C Likely pathogenic ★★ same condition
HAX1 c.557-1G>C Pathogenic/Likely pathogenic ★★ same condition
HAX1 c.663+1G>A Pathogenic/Likely pathogenic ★★ same condition
HAX1 p.Arg29Ter Pathogenic/Likely pathogenic ★★ same condition
HAX1 p.Gln201Ter Likely pathogenic ★★ same condition
HAX1 p.Glu113Ter Pathogenic/Likely pathogenic ★★ 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/hax1-p-phe7 (accessed [today's date]).

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