Is FER p.Lys86Arg (c.257A>G) pathogenic?

FER p.Lys86Arg (c.257A>G) is classified Uncertain significance in FER (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-16). AlphaMissense: likely benign (0.0787); Absent from gnomAD v4.1.

How common is FER p.Lys86Arg (c.257A>G) in the general population?

FER p.Lys86Arg (c.257A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FER p.Lys86Arg (c.257A>G)?

AlphaMissense predicts likely benign (score 0.0787) — an in-silico prediction, not a clinical call.

FER p.Lys86Arg

c.257A>G · rs2532275700 · VCV2245794

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0787 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,595,264)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0787	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -6.70	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 9.2	GERP 2.3, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 302 kb · p 0.76 · regional, not allelic
Overall
CADD	21.9	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

No allele count reported in gnomAD v4.1 (AN 1,595,264). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FER
Protein: p.Lys86Arg
Coding: c.257A>G
MANE Select: NM_005246
dbSNP: rs2532275700
Type: single nucleotide variant
Location: chr5:108832819 (GRCh38)
Gene constraint: LOEUF 0.723 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.29 · 2 PDB
Residue 86: the f-bar domain; the 'important for interaction with membranes containing phosphoinositides' region

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

Similar variants

FER p.Ala272Thr Uncertain significance ★ ⚠ same type
FER p.Ala313Gly Uncertain significance ★ ⚠ same type
FER p.Ala438Ser Uncertain significance ★ ⚠ same type
FER p.Ala89Thr Uncertain significance ★ ⚠ same type
FER p.Arg417Ser Uncertain significance ★ ⚠ same type
FER p.Arg707His Uncertain significance ★ ⚠ same type
FER p.Asn148Ile Uncertain significance ★ ⚠ same type
FER p.Asn261Ser 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/fer-p-lys86arg (accessed [today's date]).

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