Is FER p.Ser234Arg (c.700A>C) pathogenic?

FER p.Ser234Arg (c.700A>C) is classified Uncertain significance in FER (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-17). AlphaMissense: likely pathogenic (0.9731); Absent from gnomAD v4.1.

How common is FER p.Ser234Arg (c.700A>C) in the general population?

FER p.Ser234Arg (c.700A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FER p.Ser234Arg (c.700A>C)?

AlphaMissense predicts likely pathogenic (score 0.9731) — an in-silico prediction, not a clinical call.

FER p.Ser234Arg

c.700A>C · rs2532589021 · VCV2326456

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9731 · 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	0.9731	likely pathogenic
REVEL	0.441	indeterminate
SaProt	LLR -9.18	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 302 kb · p 0.76 · regional, not allelic
Overall
CADD	26.9	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: FER
Protein: p.Ser234Arg
Coding: c.700A>C
MANE Select: NM_005246
dbSNP: rs2532589021
Type: single nucleotide variant
Location: chr5:108871399 (GRCh38)
Gene constraint: LOEUF 0.723 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.29 · 2 PDB
Residue 234: 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-ser234arg (accessed [today's date]).

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