Is FERMT2 p.Ile574Ser (c.1721T>G) pathogenic?

FERMT2 p.Ile574Ser (c.1721T>G) is classified Uncertain significance in FERMT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-27). AlphaMissense: likely benign (0.1428); Absent from gnomAD v4.1.

How common is FERMT2 p.Ile574Ser (c.1721T>G) in the general population?

FERMT2 p.Ile574Ser (c.1721T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FERMT2 p.Ile574Ser (c.1721T>G)?

AlphaMissense predicts likely benign (score 0.1428) — an in-silico prediction, not a clinical call.

FERMT2 p.Ile574Ser

c.1721T>G · VCV3849957

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1428 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1428	likely benign
REVEL	0.502	indeterminate
SaProt	LLR -11.01	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 92 kb · p 7.5e-09 · regional, not allelic
Overall
CADD	25.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FERMT2
Protein: p.Ile574Ser
Coding: c.1721T>G
MANE Select: NM_006832
Type: single nucleotide variant
Location: chr14:52860347 (GRCh38)
Gene constraint: LOEUF 0.304 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.79 · 6 PDB
Residue 574: the ferm domain; a β-strand

Full FERMT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FERMT2 p.Ile574Val Uncertain significance ★ ⚠ same residue
FERMT2 c.1603-562A>G Uncertain significance ★ same type
FERMT2 c.1603-565G>C Uncertain significance ★ same type
FERMT2 c.1603-566G>C Uncertain significance ★ same type
FERMT2 p.Ala122Gly Uncertain significance ★ same type
FERMT2 p.Ala298Gly Uncertain significance ★ ⚠ same type
FERMT2 p.Ala481Val Uncertain significance ★ ⚠ same type
FERMT2 p.Ala537Val 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/fermt2-p-ile574ser (accessed [today's date]).

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