Is FERMT1 p.Ser3Pro (c.7T>C) pathogenic?

FERMT1 p.Ser3Pro (c.7T>C) is classified Uncertain significance in FERMT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-09). AlphaMissense: likely benign (0.0733); Ultra-rare (popmax 0.0147%, afr); Associated with Inborn genetic diseases.

What condition is associated with FERMT1 p.Ser3Pro (c.7T>C)?

FERMT1 p.Ser3Pro (c.7T>C) is associated with Inborn genetic diseases (ClinVar).

How common is FERMT1 p.Ser3Pro (c.7T>C) in the general population?

FERMT1 p.Ser3Pro (c.7T>C) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

What do computational predictors say about FERMT1 p.Ser3Pro (c.7T>C)?

AlphaMissense predicts likely benign (score 0.0733) — an in-silico prediction, not a clinical call.

FERMT1 p.Ser3Pro

c.7T>C · rs758985794 · VCV1495870

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0733 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0733	likely benign
REVEL	0.113	moderately benign-leaning
SaProt	LLR -6.96	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 6.5	GERP 0.93, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 42 kb · p 3.8e-05 · regional, not allelic
Overall
CADD	23.0	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 0.0147% African / African-American · 11/74,928 alleles

Filtering AF 0.00815% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.000682% 11/1,613,900 alleles · ultra-rare exomes 3/1,461,700 · genomes 8/152,200 · joint denominator

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: FERMT1
Protein: p.Ser3Pro
Coding: c.7T>C
MANE Select: NM_017671
dbSNP: rs758985794
Type: single nucleotide variant
Location: chr20:6119548 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.14

Full FERMT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FERMT1 p.Ala345Val Uncertain significance ★★ ⚠ same condition
FERMT1 p.Ala359Val Uncertain significance ★★ ⚠ same condition
FERMT1 p.Ala539Val Uncertain significance ★★ ⚠ same condition
FERMT1 p.Arg108Thr Uncertain significance ★★ ⚠ same condition
FERMT1 p.Arg17His Uncertain significance ★★ ⚠ same condition
FERMT1 p.Arg255His Uncertain significance ★★ ⚠ same condition
FERMT1 p.Arg522Trp Uncertain significance ★★ ⚠ same condition
FERMT1 p.Arg554Gln Uncertain significance ★★ ⚠ same condition

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/fermt1-p-ser3pro (accessed [today's date]).

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