Is A4GNT p.Ser93Phe (c.278C>T) pathogenic?

A4GNT p.Ser93Phe (c.278C>T) is classified Uncertain significance in A4GNT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-24). AlphaMissense: likely benign (0.1027); Ultra-rare (popmax 0.016%, afr).

How common is A4GNT p.Ser93Phe (c.278C>T) in the general population?

A4GNT p.Ser93Phe (c.278C>T) is ultra-rare (popmax 0.016%, afr) (gnomAD).

What do computational predictors say about A4GNT p.Ser93Phe (c.278C>T)?

AlphaMissense predicts likely benign (score 0.1027) — an in-silico prediction, not a clinical call.

A4GNT p.Ser93Phe

c.278C>T · VCV4119887

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1027 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1027	likely benign
REVEL	0.176	moderately benign-leaning
SaProt	LLR -8.77	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 1.7, phastCons 0.99
Regional constraint	o/e 0.90	unconstrained · MANE · 6,989 bp · p 0.05 · regional, not allelic
Overall
CADD	20.1	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 0.016% African / African-American · 12/74,902 alleles

Filtering AF 0.00922% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00722%

Overall 0.000805% 13/1,613,992 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,242
European (non-Finnish)	8.47e-05%	1,180,025

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: A4GNT
Protein: p.Ser93Phe
Coding: c.278C>T
MANE Select: NM_016161
Type: single nucleotide variant
Location: chr3:138130979 (GRCh38)
Gene constraint: LOEUF 1.375 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 89.43

Full A4GNT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

A4GNT p.Arg266Ter Likely benign ★★ same type
A4GNT p.Ala141Pro Uncertain significance ★ ⚠ same type
A4GNT p.Ala141Thr Uncertain significance ★ ⚠ same type
A4GNT p.Ala186Asp Uncertain significance ★ ⚠ same type
A4GNT p.Ala186Thr Uncertain significance ★ ⚠ same type
A4GNT p.Arg154Cys Uncertain significance ★ ⚠ same type
A4GNT p.Arg154Ser Uncertain significance ★ ⚠ same type
A4GNT p.Arg188Trp 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/a4gnt-p-ser93phe (accessed [today's date]).

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