Is ALPL p.Glu237Asp (c.711G>C) pathogenic?

ALPL p.Glu237Asp (c.711G>C) is classified Uncertain significance in ALPL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-08). AlphaMissense: likely benign (0.0958); Absent from gnomAD v4.1.

How common is ALPL p.Glu237Asp (c.711G>C) in the general population?

ALPL p.Glu237Asp (c.711G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALPL p.Glu237Asp (c.711G>C)?

AlphaMissense predicts likely benign (score 0.0958) — an in-silico prediction, not a clinical call.

ALPL p.Glu237Asp

c.711G>C · rs2545317301 · VCV2844230

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0958 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0958	likely benign
REVEL	0.333	indeterminate
SaProt	LLR -6.06	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -0.84, phastCons 0.62
Regional constraint	o/e 0.83	unconstrained · MANE · 24 kb · p 6.1e-06 · regional, not allelic
Overall
CADD	19.17	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ALPL
Protein: p.Glu237Asp
Coding: c.711G>C
MANE Select: NM_000478
dbSNP: rs2545317301
Type: single nucleotide variant
Location: chr1:21568166 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.74 · 5 PDB

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

Similar variants

ALPL c.1190-2A>T Pathogenic ★★ same type
ALPL c.182-1G>A Pathogenic/Likely pathogenic ★★ same type
ALPL c.182-2A>G Pathogenic/Likely pathogenic ★★ same type
ALPL c.297+1G>A Pathogenic/Likely pathogenic ★★ same type
ALPL c.298-1G>A Pathogenic ★★ same type
ALPL c.472+1G>A Pathogenic ★★ same type
ALPL c.62-1G>C Pathogenic/Likely pathogenic ★★ same type
ALPL c.648+1G>A 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/alpl-p-glu237asp (accessed [today's date]).

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