Is GALM p.Phe285= (c.855C>T) pathogenic?

GALM p.Phe285= (c.855C>T) is classified Benign in GALM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-13). Rare (popmax 0.163%, nfe).

How common is GALM p.Phe285= (c.855C>T) in the general population?

GALM p.Phe285= (c.855C>T) is rare (popmax 0.163%, nfe) (gnomAD).

GALM p.Phe285=

c.855C>T · rs114039092 · VCV1601208

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.163%, nfe)

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 4	GERP 1.8, phastCons 1
Overall
CADD	13.84	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.163% European (non-Finnish) · 1,928/1,179,946 alleles

Filtering AF 0.157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.155%

Overall 0.144% 2,324/1,614,058 alleles · rare exomes 2,151/1,461,788 · genomes 173/152,270 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.405%	247
European (non-Finnish)grpmax	0.163%	612
Amishnot grpmax-eligible	0.11%	912
Remaining individualsnot grpmax-eligible	0.0976%	1,025
Middle Eastern	0.0826%	1,211
Ashkenazi Jewishnot grpmax-eligible	0.0473%	2,115
Admixed American	0.0383%	2,609
South Asian	0.0209%	4,794
African / African-American	0.0187%	5,360

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe285=
Coding: c.855C>T
MANE Select: NM_138801
dbSNP: rs114039092
Type: single nucleotide variant
Location: chr2:38731813 (GRCh38)
Gene constraint: LOEUF 1.421 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.83 · 2 PDB
Residue 285: a UniProt-annotated variant site (in galac4; loss of protein accumulation)

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

Similar variants

GALM p.Phe285Ile Uncertain significance ★ same residue
GALM p.Arg131Cys Uncertain significance ★★ ⚠ same type
GALM p.Gly155Arg Uncertain significance ★★ ⚠ same type
GALM p.His333Arg Uncertain significance ★★ ⚠ same type
GALM p.Val8Met Uncertain significance ★★ ⚠ same type
GALM c.191-100G>T Benign ★★ same type
GALM c.191-128T>C Benign ★★ same type
GALM c.191-32T>A Benign ★★ 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/galm-p-phe285 (accessed [today's date]).

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