Is ALPP p.Glu37Gln (c.109G>C) pathogenic?

ALPP p.Glu37Gln (c.109G>C) is classified Benign in ALPP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-09-03). AlphaMissense: likely benign (0.0713); Low-frequency (popmax 3.41%, afr).

How common is ALPP p.Glu37Gln (c.109G>C) in the general population?

ALPP p.Glu37Gln (c.109G>C) is low-frequency (popmax 3.41%, afr) (gnomAD).

What do computational predictors say about ALPP p.Glu37Gln (c.109G>C)?

AlphaMissense predicts likely benign (score 0.0713) — an in-silico prediction, not a clinical call.

ALPP p.Glu37Gln

c.109G>C · rs113323105 · VCV773651

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0713 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.41%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0713	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -4.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.96	GERP -3.7, phastCons 0.13
Regional constraint	o/e 0.97	unconstrained · MANE · 1,678 bp · p 0.53 · regional, not allelic
Overall
CADD	0.08	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 3.41% African / African-American · 2,547/74,732 alleles

Filtering AF 3.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.25%

Overall 1.26% 20,323/1,613,576 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.41%	29
East Asian	3.01%	33
South Asian	2.93%	34
Remaining individualsnot grpmax-eligible	1.27%	79
European (non-Finnish)	1.03%	97
Middle Eastern	0.677%	148
Admixed American	0.603%	166
Finnishnot grpmax-eligible	0.422%	237
Ashkenazi Jewishnot grpmax-eligible	0.341%	293

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: ALPP
Protein: p.Glu37Gln
Coding: c.109G>C
MANE Select: NM_001632
dbSNP: rs113323105
Type: single nucleotide variant
Location: chr2:232379003 (GRCh38)
Gene constraint: LOEUF 1.117 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.73 · 8 PDB
Residue 37: an α-helix

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

Similar variants

ALPP c.865+8C>T Likely benign ★★ same type
ALPP p.Ala176= Benign ★★ same type
ALPP p.Arg231Pro Benign ★★ same type
ALPP p.Arg36= Benign ★★ same type
ALPP p.Gly233= Likely benign ★★ same type
ALPP p.Gly63= Likely benign ★★ same type
ALPP p.Phe331= Benign ★★ same type
ALPP p.Ser192Trp Likely 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/alpp-p-glu37gln (accessed [today's date]).

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