Is FER p.Asp19His (c.55G>C) pathogenic?

FER p.Asp19His (c.55G>C) is classified Uncertain significance in FER (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-17). AlphaMissense: likely pathogenic (0.8727); Absent from gnomAD v4.1.

How common is FER p.Asp19His (c.55G>C) in the general population?

FER p.Asp19His (c.55G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FER p.Asp19His (c.55G>C)?

AlphaMissense predicts likely pathogenic (score 0.8727) — an in-silico prediction, not a clinical call.

FER p.Asp19His

c.55G>C · rs2532036664 · VCV2548182

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8727 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8727	likely pathogenic
REVEL	0.496	indeterminate
SaProt	LLR -11.13	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 302 kb · p 0.76 · regional, not allelic
Overall
CADD	28.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: FER
Protein: p.Asp19His
Coding: c.55G>C
MANE Select: NM_005246
dbSNP: rs2532036664
Type: single nucleotide variant
Location: chr5:108798237 (GRCh38)
Gene constraint: LOEUF 0.723 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.29 · 2 PDB
Residue 19: 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-asp19his (accessed [today's date]).

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