Is PHYKPL p.Ala139= (c.417G>A) pathogenic?

PHYKPL p.Ala139= (c.417G>A) is classified Likely benign in PHYKPL (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-06-19). Rare (popmax 0.369%, afr); Associated with PHYKPL-related disorder.

What condition is associated with PHYKPL p.Ala139= (c.417G>A)?

PHYKPL p.Ala139= (c.417G>A) is associated with PHYKPL-related disorder (ClinVar).

How common is PHYKPL p.Ala139= (c.417G>A) in the general population?

PHYKPL p.Ala139= (c.417G>A) is rare (popmax 0.369%, afr) (gnomAD).

PHYKPL p.Ala139=

c.417G>A · rs114298500 · VCV3033251

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.369%, afr)

Conditions

PHYKPL-related disorder

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 -0.6	GERP -3.7
Overall
CADD	4.95	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.369% African / African-American · 277/75,042 alleles

Filtering AF 0.333% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.319%

Overall 0.0197% 317/1,612,786 alleles · rare exomes 166/1,460,474 · genomes 151/152,312 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.369%	271
Remaining individualsnot grpmax-eligible	0.0336%	2,974
Middle Eastern	0.0165%	6,058
Admixed American	0.00667%	15,002
South Asian	0.00549%	18,204
East Asian	0.00223%	44,850
European (non-Finnish)	0.000679%	147,365

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: PHYKPL
Protein: p.Ala139=
Coding: c.417G>A
MANE Select: NM_153373
dbSNP: rs114298500
Type: single nucleotide variant
Location: chr5:178224726 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.20

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

Disease context

PHYKPL-related disorder

Similar variants

PHYKPL p.Ala139Val Uncertain significance ★ ⚠ same residue
PHYKPL c.502-6C>T Likely benign same condition
PHYKPL p.Ala212Thr Benign same condition
PHYKPL p.His126Arg Benign same condition
PHYKPL p.Ile356= Likely benign same condition
PHYKPL p.Leu392= Likely benign same condition
PHYKPL p.Thr11= Benign same condition
PHYKPL p.Glu437Val Uncertain significance ★★ ⚠ same type

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/phykpl-p-ala139 (accessed [today's date]).

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