Is FUT6 p.Pro124Ser (c.370C>T) pathogenic?

FUT6 p.Pro124Ser (c.370C>T) is classified Benign in FUT6 (ClinVar, Multiple submitters, 2 submitters). AlphaMissense: likely benign (0.1308); Common (popmax 60.3%, afr) — too common for a highly-penetrant pathogenic allele; Associated with fucosyltransferase 6 deficiency.

What condition is associated with FUT6 p.Pro124Ser (c.370C>T)?

FUT6 p.Pro124Ser (c.370C>T) is associated with fucosyltransferase 6 deficiency (ClinVar).

What do computational predictors say about FUT6 p.Pro124Ser (c.370C>T)?

AlphaMissense predicts likely benign (score 0.1308) — an in-silico prediction, not a clinical call.

FUT6 p.Pro124Ser

Q: How common is FUT6 p.Pro124Ser (c.370C>T) in the general population?

FUT6 p.Pro124Ser (c.370C>T) is common (popmax 60.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.370C>T · rs778805 · VCV979161

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1308 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 60.3%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

fucosyltransferase 6 deficiency

Computational evidence

Protein change
AlphaMissense	0.1308	likely benign
REVEL	0.107	moderately benign-leaning
SaProt	LLR -10.74	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 3.3	GERP -2.4, phastCons 0.76
Regional constraint	o/e 0.92	unconstrained · MANE · 1,076 bp · p 0.068 · regional, not allelic
Overall
CADD	4.92	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 60.3% African / African-American · 45,170/74,900 alleles

Filtering AF 59.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 59.6%

Overall 35.3% 569,658/1,613,530 alleles · common exomes 503,526/1,461,642 · genomes 66,132/151,888 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	60.3%	2
East Asian	57.3%	2
Admixed American	51.5%	2
South Asian	39.2%	3
Finnishnot grpmax-eligible	38.9%	3
Ashkenazi Jewishnot grpmax-eligible	38.9%	3
Remaining individualsnot grpmax-eligible	37%	3
Middle Eastern	34.5%	3
European (non-Finnish)	31.4%	3
Amishnot grpmax-eligible	23.5%	4

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.Pro124Ser
Coding: c.370C>T
MANE Select: NM_000150
dbSNP: rs778805
Type: single nucleotide variant
Location: chr19:5832198 (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

Disease context

fucosyltransferase 6 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FUT6 p.Pro124Arg Uncertain significance ★ ⚠ same residue
FUT6 p.Arg303Gly Benign ★★ same condition
FUT6 p.Glu247Lys Uncertain significance ★ ⚠ same condition
FUT6 p.Tyr315Ter Conflicting classifications of pathogenicity ★ same condition
FUT6 p.Ala195= Likely benign ★★ same type
FUT6 p.Ala104Gly Uncertain significance ★ ⚠ same type
FUT6 p.Ala104Thr Uncertain significance ★ ⚠ same type
FUT6 p.Ala104Val 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-pro124ser (accessed [today's date]).

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