Is GAL p.Pro27= (c.81G>A) pathogenic?

GAL p.Pro27= (c.81G>A) is classified Uncertain significance in GAL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-28). Ultra-rare (popmax 0.0337%, mid).

How common is GAL p.Pro27= (c.81G>A) in the general population?

GAL p.Pro27= (c.81G>A) is ultra-rare (popmax 0.0337%, mid) (gnomAD).

GAL p.Pro27=

c.81G>A · VCV3366545

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0337%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.059	GERP 0.94, phastCons 0.58
Overall
CADD	17.73	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0337% Middle Eastern · 2/5,942 alleles

Filtering AF 0.00593% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00246%

Overall 0.00189% 30/1,586,002 alleles · ultra-rare exomes 28/1,433,760 · genomes 2/152,242 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0337%	2,971
Remaining individualsnot grpmax-eligible	0.0147%	6,820
Admixed American	0.00344%	29,107
European (non-Finnish)	0.00146%	68,441

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: GAL
Protein: p.Pro27=
Coding: c.81G>A
MANE Select: NM_015973
Type: single nucleotide variant
Location: chr11:68685004 (GRCh38)
Structure: AlphaFold pLDDT 66.71

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

Similar variants

GALP p.Ala27Thr Uncertain significance ★ ⚠ same residue
GALP p.Ala27Val Likely benign ★ same residue
GAL p.Ala10Thr Uncertain significance ★★ ⚠ same type
GAL p.Ala15Thr Uncertain significance ★★ ⚠ same type
GAL p.Arg52Gly Uncertain significance ★★ ⚠ same type
GAL p.Arg67Trp Uncertain significance ★★ ⚠ same type
GAL p.Arg88His Uncertain significance ★★ ⚠ same type
GAL p.Asp106Asn Uncertain significance ★★ ⚠ 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/gal-p-pro27 (accessed [today's date]).

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