Is ALX4 p.Ala320Ser (c.958G>T) pathogenic?

ALX4 p.Ala320Ser (c.958G>T) is classified Uncertain significance in ALX4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). AlphaMissense: likely benign (0.0781); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ALX4 p.Ala320Ser (c.958G>T)?

ALX4 p.Ala320Ser (c.958G>T) is associated with Inborn genetic diseases (ClinVar).

How common is ALX4 p.Ala320Ser (c.958G>T) in the general population?

ALX4 p.Ala320Ser (c.958G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALX4 p.Ala320Ser (c.958G>T)?

AlphaMissense predicts likely benign (score 0.0781) — an in-silico prediction, not a clinical call.

ALX4 p.Ala320Ser

c.958G>T · VCV4090269

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0781 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0781	likely benign
REVEL	0.353	indeterminate
SaProt	LLR -5.11	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 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 45 kb · p 0.71 · regional, not allelic
Overall
CADD	20.4	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: ALX4
Protein: p.Ala320Ser
Coding: c.958G>T
MANE Select: NM_021926
Type: single nucleotide variant
Location: chr11:44265132 (GRCh38)
Gene constraint: LOEUF 0.902 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.00 · 4 PDB

Full ALX4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ALX4 p.Arg265Ter Pathogenic ★★ same condition
ALX4 p.Arg193Gln Uncertain significance ★★ ⚠ same condition
ALX4 p.Arg257His Uncertain significance ★★ ⚠ same condition
ALX4 p.Arg388His Uncertain significance ★★ ⚠ same condition
ALX4 p.Asp176Gly Uncertain significance ★★ ⚠ same condition
ALX4 p.Asp206Asn Uncertain significance ★★ ⚠ same condition
ALX4 p.Cys331Tyr Uncertain significance ★★ ⚠ same condition
ALX4 p.Gln104Pro Uncertain significance ★★ ⚠ same condition

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/alx4-p-ala320ser (accessed [today's date]).

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