Is FUT6 p.Ser48Pro (c.142T>C) pathogenic?

FUT6 p.Ser48Pro (c.142T>C) is classified Uncertain significance in FUT6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). AlphaMissense: likely benign (0.0652); Ultra-rare (popmax 0.056%, sas).

How common is FUT6 p.Ser48Pro (c.142T>C) in the general population?

FUT6 p.Ser48Pro (c.142T>C) is ultra-rare (popmax 0.056%, sas) (gnomAD).

What do computational predictors say about FUT6 p.Ser48Pro (c.142T>C)?

AlphaMissense predicts likely benign (score 0.0652) — an in-silico prediction, not a clinical call.

FUT6 p.Ser48Pro

c.142T>C · rs780771178 · VCV3097513

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0652 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.056%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0652	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -6.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.44	GERP -1.9
Regional constraint	o/e 0.92	unconstrained · MANE · 1,076 bp · p 0.068 · regional, not allelic
Overall
CADD	1.242	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.056% South Asian · 51/91,062 alleles

Filtering AF 0.0437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0394%

Overall 0.00409% 66/1,613,652 alleles · ultra-rare exomes 64/1,461,736 · genomes 2/151,916 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.056%	1,786
Remaining individualsnot grpmax-eligible	0.0224%	4,463
European (non-Finnish)	8.47e-05%	1,179,954

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.Ser48Pro
Coding: c.142T>C
MANE Select: NM_000150
dbSNP: rs780771178
Type: single nucleotide variant
Location: chr19:5832426 (GRCh38)
Gene constraint: LOEUF 1.841 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 89.81

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

Similar variants

FUT6 p.Ala195= Likely benign ★★ same type
FUT6 p.Arg303Gly Benign ★★ same type
FUT6 p.Pro124Ser 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-ser48pro (accessed [today's date]).

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