Is PFKL p.Phe308= (c.924C>T) pathogenic?

PFKL p.Phe308= (c.924C>T) is classified Likely benign in PFKL (ClinVar, Single submitter, 2 submitters; last evaluated 2022-03-01). Rare (popmax 0.202%, nfe).

How common is PFKL p.Phe308= (c.924C>T) in the general population?

PFKL p.Phe308= (c.924C>T) is rare (popmax 0.202%, nfe) (gnomAD).

PFKL p.Phe308=

c.924C>T · rs139920536 · VCV2652742

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.202%, nfe)

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 -10	GERP -3.9
Overall
CADD	2.414	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.202% European (non-Finnish) · 2,363/1,169,768 alleles

Filtering AF 0.195% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.192%

Overall 0.179% 2,851/1,597,026 alleles · rare exomes 2,484/1,444,750 · genomes 367/152,276 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.522%	192
European (non-Finnish)grpmax	0.202%	495
Remaining individualsnot grpmax-eligible	0.133%	753
Ashkenazi Jewishnot grpmax-eligible	0.111%	898
Admixed American	0.0555%	1,802
Middle Eastern	0.0374%	2,677
African / African-American	0.016%	6,235
South Asian	0.00224%	44,673

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PFKL
Protein: p.Phe308=
Coding: c.924C>T
MANE Select: NM_002626
dbSNP: rs139920536
Type: single nucleotide variant
Location: chr21:44316512 (GRCh38)
Gene constraint: LOEUF 1.028 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.53 · 5 PDB
Residue 308: the 'n-terminal catalytic pfk domain 1' region; an α-helix

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

Similar variants

PFKL p.Arg513Cys Uncertain significance ★★ ⚠ same type
PFKL p.Glu738Lys Uncertain significance ★★ ⚠ same type
PFKL p.Pro332Leu Uncertain significance ★★ ⚠ same type
PFKL p.Val59Met Uncertain significance ★★ ⚠ same type
PFKL c.747+7G>A Benign ★★ same type
PFKL p.Ala320= Likely benign ★★ same type
PFKL p.Arg621= Benign ★★ same type
PFKL p.Asp237Val Benign ★★ ⚠ 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/pfkl-p-phe308 (accessed [today's date]).

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