Is GALM p.Lys89Asn (c.267G>C) pathogenic?

GALM p.Lys89Asn (c.267G>C) is classified Uncertain significance in GALM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-02). AlphaMissense: likely benign (0.21); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with GALM p.Lys89Asn (c.267G>C)?

GALM p.Lys89Asn (c.267G>C) is associated with Inborn genetic diseases (ClinVar).

How common is GALM p.Lys89Asn (c.267G>C) in the general population?

GALM p.Lys89Asn (c.267G>C) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about GALM p.Lys89Asn (c.267G>C)?

AlphaMissense predicts likely benign (score 0.21) — an in-silico prediction, not a clinical call.

GALM p.Lys89Asn

c.267G>C · rs1255611902 · VCV2331846

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.21 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.21	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -8.55	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 -14	GERP -3.5
Regional constraint	o/e 1.09	unconstrained · MANE · 67 kb · p 0.071 · regional, not allelic
Overall
CADD	0.243	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

Grpmax group 0.00267% African / African-American · 2/74,902 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000248% 4/1,613,976 alleles · very rare exomes 2/1,461,848 · genomes 2/152,128 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,451
European (non-Finnish)	0.000169%	590,005

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: GALM
Protein: p.Lys89Asn
Coding: c.267G>C
MANE Select: NM_138801
dbSNP: rs1255611902
Type: single nucleotide variant
Location: chr2:38675988 (GRCh38)
Gene constraint: LOEUF 1.421 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.83 · 2 PDB
Residue 89: a UniProt-annotated variant site (in galac4; loss of protein accumulation); a β-strand

Full GALM 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

GALM p.Gly155Arg Uncertain significance ★★ ⚠ same condition
GALM p.His333Arg Uncertain significance ★★ ⚠ same condition
GALM p.Val8Met Uncertain significance ★★ ⚠ same condition
GALM p.Ala163Pro Uncertain significance ★ ⚠ same condition
GALM p.Ala198Gly Uncertain significance ★ ⚠ same condition
GALM p.Asn245Asp Uncertain significance ★ ⚠ same condition
GALM p.Asp199Ala Uncertain significance ★ ⚠ same condition
GALM p.Asp32Tyr 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/galm-p-lys89asn (accessed [today's date]).

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