Is HEXA p.Ala20Ser (c.58G>T) pathogenic?

HEXA p.Ala20Ser (c.58G>T) is classified Uncertain significance in HEXA (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-27). AlphaMissense: likely benign (0.1135); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with HEXA p.Ala20Ser (c.58G>T)?

HEXA p.Ala20Ser (c.58G>T) is associated with Inborn genetic diseases (ClinVar).

How common is HEXA p.Ala20Ser (c.58G>T) in the general population?

HEXA p.Ala20Ser (c.58G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HEXA p.Ala20Ser (c.58G>T)?

AlphaMissense predicts likely benign (score 0.1135) — an in-silico prediction, not a clinical call.

HEXA p.Ala20Ser

c.58G>T · VCV4858348

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1135 · 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	0.1135	likely benign
REVEL	0.331	indeterminate
SaProt	LLR -6.91	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 0.84	GERP 0.48, phastCons 0.001
Regional constraint	o/e 0.99	unconstrained · MANE · 32 kb · p 0.87 · regional, not allelic
Overall
CADD	12.23	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: HEXA
Protein: p.Ala20Ser
Coding: c.58G>T
MANE Select: NM_000520
Type: single nucleotide variant
Location: chr15:72375915 (GRCh38)
Gene constraint: LOEUF 0.947 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.62 · 2 PDB

Full HEXA 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

HEXA p.Ala20Gly Uncertain significance ★ ⚠ same residue
HEXA p.Ala20Val Uncertain significance ★ ⚠ same residue
HEXA p.Ala20= Likely benign ★ same residue
HEXA p.Arg170Trp Pathogenic/Likely pathogenic ★★ same condition
HEXA p.Arg499Cys Pathogenic ★★ same condition
HEXA p.Arg499His Pathogenic ★★ same condition
HEXA p.Glu482Lys Pathogenic/Likely pathogenic ★★ same condition
HEXA p.Ala194Val 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/hexa-p-ala20ser (accessed [today's date]).

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