Is PFKL p.Asp237Val (c.710A>T) pathogenic?

PFKL p.Asp237Val (c.710A>T) is classified Benign in PFKL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-11-15). AlphaMissense: likely benign (0.1155); Common (popmax 10.8%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about PFKL p.Asp237Val (c.710A>T)?

AlphaMissense predicts likely benign (score 0.1155) — an in-silico prediction, not a clinical call.

PFKL p.Asp237Val

Q: How common is PFKL p.Asp237Val (c.710A>T) in the general population?

PFKL p.Asp237Val (c.710A>T) is common (popmax 10.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.710A>T · rs1057037 · VCV440034

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1155 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 10.8%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1155	likely benign
REVEL	0.338	indeterminate
SaProt	LLR -11.48	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.25	donor loss · deltas
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 27 kb · p 0.008 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.8% African / African-American · 8,119/74,942 alleles

Filtering AF 10.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.6%

Overall 7.88% 126,649/1,607,110 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	10.8%	9
South Asian	10.1%	10
Middle Eastern	9.59%	10
Ashkenazi Jewishnot grpmax-eligible	8.01%	12
European (non-Finnish)	7.86%	13
Remaining individualsnot grpmax-eligible	7.82%	13
Finnishnot grpmax-eligible	7.14%	14
Admixed American	7.13%	14
Amishnot grpmax-eligible	6.47%	15
East Asian	0.776%	129

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.Asp237Val
Coding: c.710A>T
MANE Select: NM_002626
dbSNP: rs1057037
Type: single nucleotide variant
Location: chr21:44313984 (GRCh38)
Gene constraint: LOEUF 1.028 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.53 · 5 PDB
Residue 237: the 'n-terminal catalytic pfk domain 1' region; a UniProt-annotated variant site (in)

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.Leu122= 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-asp237val (accessed [today's date]).

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