Is PHYH p.Tyr239= (c.717C>T) pathogenic?

PHYH p.Tyr239= (c.717C>T) is classified Benign/Likely benign in PHYH (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-26). Rare (popmax 0.804%, afr); Associated with adult Refsum disease.

What condition is associated with PHYH p.Tyr239= (c.717C>T)?

PHYH p.Tyr239= (c.717C>T) is associated with adult Refsum disease (ClinVar).

How common is PHYH p.Tyr239= (c.717C>T) in the general population?

PHYH p.Tyr239= (c.717C>T) is rare (popmax 0.804%, afr) (gnomAD).

How is Adult Refsum disease inherited?

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

PHYH p.Tyr239=

c.717C>T · rs142720126 · VCV167468

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.804%, afr)

Conditions

adult Refsum disease

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 -0.36	GERP -3.4
Overall
CADD	0.648	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.804% African / African-American · 603/75,002 alleles

Filtering AF 0.751% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.73%

Overall 0.0428% 691/1,613,930 alleles · rare exomes 342/1,461,774 · genomes 349/152,156 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.804%	124
Middle Eastern	0.132%	758
Admixed American	0.0433%	2,308
Remaining individualsnot grpmax-eligible	0.0384%	2,604
South Asian	0.00549%	18,212
Finnishnot grpmax-eligible	0.00312%	32,008
East Asian	0.00223%	44,864
European (non-Finnish)	0.00186%	53,632

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: PHYH
Protein: p.Tyr239=
Coding: c.717C>T
MANE Select: NM_006214
dbSNP: rs142720126
Type: single nucleotide variant
Location: chr10:13283801 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.33 · 1 PDB

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

Disease context

adult Refsum disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Adult Refsum disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

PHYH p.Tyr239Ter Pathogenic ★ same residue
PHYH c.134+1G>A Likely pathogenic ★★ same condition
PHYH c.135-1G>C Pathogenic/Likely pathogenic ★★ same condition
PHYH c.135-2A>G Pathogenic ★★ same condition
PHYH c.497-1G>A Likely pathogenic ★★ same condition
PHYH c.497-2A>G Pathogenic/Likely pathogenic ★★ same condition
PHYH c.678+2T>C Likely pathogenic ★★ same condition
PHYH p.Ala277Glu 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/phyh-p-tyr239 (accessed [today's date]).

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