Is FER p.Ser745= (c.2235C>T) pathogenic?

FER p.Ser745= (c.2235C>T) is classified Benign in FER (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). Common (popmax 7.92%, afr) — too common for a highly-penetrant pathogenic allele.

FER p.Ser745=

Q: How common is FER p.Ser745= (c.2235C>T) in the general population?

FER p.Ser745= (c.2235C>T) is common (popmax 7.92%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2235C>T · rs55876507 · VCV776052

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 7.92%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.26	phastCons 0.98
Overall
CADD	14.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.92% African / African-American · 5,940/75,020 alleles

Filtering AF 7.75% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.68%

Overall 0.429% 6,917/1,614,098 alleles · common exomes 3,533/1,461,838 · genomes 3,384/152,260 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.92%	13
Middle Eastern	0.561%	178
Remaining individualsnot grpmax-eligible	0.541%	185
Admixed American	0.466%	214
Ashkenazi Jewishnot grpmax-eligible	0.199%	502
European (non-Finnish)	0.0214%	4,664
South Asian	0.0143%	7,006

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.Ser745=
Coding: c.2235C>T
MANE Select: NM_005246
dbSNP: rs55876507
Type: single nucleotide variant
Location: chr5:109186231 (GRCh38)
Gene constraint: LOEUF 0.723 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.29 · 2 PDB
Residue 745: the protein kinase domain

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-ser745 (accessed [today's date]).

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