Is ERFE p.Phe108= (c.324C>T) pathogenic?

ERFE p.Phe108= (c.324C>T) is classified Likely benign in ERFE (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-01). Ultra-rare (popmax 0.0137%, amr).

How common is ERFE p.Phe108= (c.324C>T) in the general population?

ERFE p.Phe108= (c.324C>T) is ultra-rare (popmax 0.0137%, amr) (gnomAD).

ERFE p.Phe108=

c.324C>T · rs1433729964 · VCV2652062

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0137%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.9	GERP -2.8
Overall
CADD	2.516	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0137% Admixed American · 7/50,974 alleles

Filtering AF 0.00639% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00455%

Overall 0.00402% 62/1,543,494 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0137%	7,282
Remaining individualsnot grpmax-eligible	0.0134%	7,483
European (non-Finnish)	0.00412%	24,268

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: ERFE
Protein: p.Phe108=
Coding: c.324C>T
MANE Select: NM_001291832
dbSNP: rs1433729964
Type: single nucleotide variant
Location: chr2:238162738 (GRCh38)
Gene constraint: LOEUF 1.697 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.15
Residue 108: the 'disordered' region

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

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/erfe-p-phe108 (accessed [today's date]).

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