Is FER p.Ser340Pro (c.1018T>C) pathogenic?

FER p.Ser340Pro (c.1018T>C) is classified Uncertain significance in FER (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-18). AlphaMissense: ambiguous (0.5413); Ultra-rare (popmax 0.0202%, eas).

How common is FER p.Ser340Pro (c.1018T>C) in the general population?

FER p.Ser340Pro (c.1018T>C) is ultra-rare (popmax 0.0202%, eas) (gnomAD).

What do computational predictors say about FER p.Ser340Pro (c.1018T>C)?

AlphaMissense predicts ambiguous (score 0.5413) — an in-silico prediction, not a clinical call.

FER p.Ser340Pro

c.1018T>C · VCV4024394

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5413 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0202%, eas)

Computational evidence

Protein change
AlphaMissense	0.5413	ambiguous
REVEL	0.392	indeterminate
SaProt	LLR -11.40	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 302 kb · p 0.76 · regional, not allelic
Overall
CADD	25.5	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

Grpmax group 0.0202% East Asian · 9/44,538 alleles

Filtering AF 0.0105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00784%

Overall 0.000561% 9/1,605,356 alleles · ultra-rare exomes 8/1,453,352 · genomes 1/152,004 · 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: FER
Protein: p.Ser340Pro
Coding: c.1018T>C
MANE Select: NM_005246
Type: single nucleotide variant
Location: chr5:108883490 (GRCh38)
Gene constraint: LOEUF 0.723 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.29 · 2 PDB

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-ser340pro (accessed [today's date]).

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