Is DHPS p.Leu24Phe (c.72G>T) pathogenic?

DHPS p.Leu24Phe (c.72G>T) is classified Uncertain significance in DHPS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-02). AlphaMissense: likely benign (0.1718); Ultra-rare (popmax 0.0344%, nfe).

How common is DHPS p.Leu24Phe (c.72G>T) in the general population?

DHPS p.Leu24Phe (c.72G>T) is ultra-rare (popmax 0.0344%, nfe) (gnomAD).

What do computational predictors say about DHPS p.Leu24Phe (c.72G>T)?

AlphaMissense predicts likely benign (score 0.1718) — an in-silico prediction, not a clinical call.

DHPS p.Leu24Phe

c.72G>T · VCV3501432

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1718 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0344%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1718	likely benign
REVEL	0.131	moderately benign-leaning
SaProt	LLR -10.06	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.21	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 0.81	GERP 1.7, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 5,925 bp · p 0.58 · regional, not allelic
Overall
CADD	20.9	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 0.0344% European (non-Finnish) · 406/1,180,046 alleles

Filtering AF 0.0316% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0305%

Overall 0.0266% 430/1,613,932 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0344%	2,907
Admixed American	0.0183%	5,455
Remaining individualsnot grpmax-eligible	0.016%	6,248
African / African-American	0.00267%	37,478
South Asian	0.0011%	91,092

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: DHPS
Protein: p.Leu24Phe
Coding: c.72G>T
MANE Select: NM_001930
Type: single nucleotide variant
Location: chr19:12681695 (GRCh38)
Gene constraint: LOEUF 0.824 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.95 · 89 PDB
Residue 24: an α-helix

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

Similar variants

DHPS p.Glu71Lys Uncertain significance ★★ ⚠ same type
DHPS p.Gly162Arg Uncertain significance ★★ ⚠ same type
DHPS p.Met124Leu Uncertain significance ★★ ⚠ same type
DHPS c.784+8G>T Likely benign ★★ same type
DHPS p.Lys358= Likely benign ★★ same type
DHPS p.Thr88= Likely benign ★★ same type
DHPS c.785-1G>C Likely pathogenic ★ same type
DHPS p.Gln194Ter Likely pathogenic ★ 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/dhps-p-leu24phe (accessed [today's date]).

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