Is FERMT1 p.Ser207Arg (c.619A>C) pathogenic?

FERMT1 p.Ser207Arg (c.619A>C) is classified Uncertain significance in FERMT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-12). AlphaMissense: likely benign (0.283); Absent from gnomAD v4.1.

How common is FERMT1 p.Ser207Arg (c.619A>C) in the general population?

FERMT1 p.Ser207Arg (c.619A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FERMT1 p.Ser207Arg (c.619A>C)?

AlphaMissense predicts likely benign (score 0.283) — an in-silico prediction, not a clinical call.

FERMT1 p.Ser207Arg

c.619A>C · rs1982915153 · VCV1508165

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.283 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.283	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -7.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.39 · evaluated, not missing
Pangolin	Δ0.21	gain · loss 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 1.3	GERP 1.1, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 42 kb · p 3.8e-05 · regional, not allelic
Overall
CADD	23.1	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

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: FERMT1
Protein: p.Ser207Arg
Coding: c.619A>C
MANE Select: NM_017671
dbSNP: rs1982915153
Type: single nucleotide variant
Location: chr20:6110425 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.14
Residue 207: the ferm domain

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

Similar variants

FERMT1 p.Ser207Asn Uncertain significance ★★ ⚠ same residue
FERMT1 c.1371+4A>G Pathogenic ★★ same type
FERMT1 c.532+1G>A Likely pathogenic ★★ same type
FERMT1 p.Arg110Ter Pathogenic ★★ same type
FERMT1 p.Arg271Ter Pathogenic ★★ same type
FERMT1 p.Arg288Ter Pathogenic ★★ same type
FERMT1 p.Glu304Ter Pathogenic ★★ same type
FERMT1 p.Trp298Ter Pathogenic ★★ 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/fermt1-p-ser207arg (accessed [today's date]).

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