Is FUT6 p.Pro124Arg (c.371C>G) pathogenic?

FUT6 p.Pro124Arg (c.371C>G) is classified Uncertain significance in FUT6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-20). AlphaMissense: likely benign (0.1052); Very rare (popmax 0.00333%, amr).

How common is FUT6 p.Pro124Arg (c.371C>G) in the general population?

FUT6 p.Pro124Arg (c.371C>G) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about FUT6 p.Pro124Arg (c.371C>G)?

AlphaMissense predicts likely benign (score 0.1052) — an in-silico prediction, not a clinical call.

FUT6 p.Pro124Arg

c.371C>G · VCV3280205

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1052 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1052	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -10.73	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -2.7, phastCons 0.59
Regional constraint	o/e 0.92	unconstrained · MANE · 1,076 bp · p 0.068 · regional, not allelic
Overall
CADD	9.665	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,004 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000186% 3/1,613,806 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,002
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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: FUT6
Protein: p.Pro124Arg
Coding: c.371C>G
MANE Select: NM_000150
Type: single nucleotide variant
Location: chr19:5832197 (GRCh38)
Gene constraint: LOEUF 1.841 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 89.81
Residue 124: a UniProt-annotated variant site (found in individuals with plasma alpha(1,3)-fucosyltransferase deficiency and no clinically relevant phenotype; results in partial enzyme inactivation; complete enzyme inactivation when associated with v-244 and g-303)

Full FUT6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FUT6 p.Pro124Ser Benign ★★ ⚠ same residue
FUT6 p.Ala195= Likely benign ★★ same type
FUT6 p.Arg303Gly Benign ★★ same type
FUT6 p.Ala104Gly Uncertain significance ★ ⚠ same type
FUT6 p.Ala104Thr Uncertain significance ★ ⚠ same type
FUT6 p.Ala104Val Uncertain significance ★ ⚠ same type
FUT6 p.Ala187Gly Uncertain significance ★ ⚠ same type
FUT6 p.Ala263Thr 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/fut6-p-pro124arg (accessed [today's date]).

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