Is GAL p.Pro68= (c.204C>T) pathogenic?

GAL p.Pro68= (c.204C>T) is classified Likely benign in GAL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-07). Ultra-rare (popmax 0.0165%, sas).

How common is GAL p.Pro68= (c.204C>T) in the general population?

GAL p.Pro68= (c.204C>T) is ultra-rare (popmax 0.0165%, sas) (gnomAD).

GAL p.Pro68=

c.204C>T · VCV4912820

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, sas)

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 -9.6	GERP -2.8
Overall
CADD	0.203	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% South Asian · 15/91,000 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00812%

Overall 0.00155% 25/1,610,618 alleles · ultra-rare exomes 24/1,458,488 · genomes 1/152,130 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0165%	6,067
Middle Eastern	0.0164%	6,082
European (non-Finnish)	0.000765%	130,796

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.Pro68=
Coding: c.204C>T
MANE Select: NM_015973
Type: single nucleotide variant
Location: chr11:68688081 (GRCh38)
Structure: AlphaFold pLDDT 66.71

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

Similar variants

GAL p.Pro68Ser Uncertain significance ★ ⚠ 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
GAL p.Asp106His 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-pro68 (accessed [today's date]).

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