Is PHYKPL p.Thr11= (c.33G>C) pathogenic?

PHYKPL p.Thr11= (c.33G>C) is classified Benign in PHYKPL (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-11). Common (popmax 31.3%, afr) — too common for a highly-penetrant pathogenic allele; Associated with PHYKPL-related disorder.

What condition is associated with PHYKPL p.Thr11= (c.33G>C)?

PHYKPL p.Thr11= (c.33G>C) is associated with PHYKPL-related disorder (ClinVar).

PHYKPL p.Thr11=

Q: How common is PHYKPL p.Thr11= (c.33G>C) in the general population?

PHYKPL p.Thr11= (c.33G>C) is common (popmax 31.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.33G>C · rs116735771 · VCV3055399

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 31.3%, afr) — too common for a highly-penetrant pathogenic allele

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 -3.5	GERP -1.6
Overall
CADD	1.002	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 31.3% African / African-American · 20,378/65,164 alleles

Filtering AF 30.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 30.8%

Overall 8.6% 114,649/1,332,518 alleles · common exomes 94,099/1,180,902 · genomes 20,550/151,616 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	31.3%	3
East Asian	9.6%	10
South Asian	9.59%	10
Remaining individualsnot grpmax-eligible	9.35%	11
Middle Eastern	9.04%	11
European (non-Finnish)	7.32%	14
Ashkenazi Jewishnot grpmax-eligible	6.76%	15
Admixed American	6.17%	16
Amishnot grpmax-eligible	5.56%	18
Finnishnot grpmax-eligible	4.68%	21

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.Thr11=
Coding: c.33G>C
MANE Select: NM_153373
dbSNP: rs116735771
Type: single nucleotide variant
Location: chr5:178232518 (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 c.502-6C>T Likely benign same condition
PHYKPL p.Ala139= 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.Glu437Val Uncertain significance ★★ ⚠ same type
PHYKPL p.Ala139Val 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-thr11 (accessed [today's date]).

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