Is FTL p.Phe167= (c.501C>T) pathogenic?

FTL p.Phe167= (c.501C>T) is classified Likely benign in FTL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-29). Ultra-rare (popmax 0.0286%, sas); Associated with hereditary hyperferritinemia with congenital cataracts.

How common is FTL p.Phe167= (c.501C>T) in the general population?

FTL p.Phe167= (c.501C>T) is ultra-rare (popmax 0.0286%, sas) (gnomAD).

FTL p.Phe167=

Q: What condition is associated with FTL p.Phe167= (c.501C>T)?

FTL p.Phe167= (c.501C>T) is associated with hereditary hyperferritinemia with congenital cataracts, neuroferritinopathy (ClinVar).

Q: How is Hereditary hyperferritinemia-cataract syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.501C>T · rs759937926 · VCV2200495

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0286%, sas)

Conditions

hereditary hyperferritinemia with congenital cataracts

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.068	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.21	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -4.4
Overall
CADD	13.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0286% South Asian · 26/91,044 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0171%

Overall 0.00452% 73/1,613,360 alleles · ultra-rare exomes 71/1,461,248 · genomes 2/152,112 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0286%	3,502
European (non-Finnish)	0.00364%	27,441
Remaining individualsnot grpmax-eligible	0.0032%	31,202
East Asian	0.00223%	44,904
Admixed American	0.00167%	59,984

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: FTL
Protein: p.Phe167=
Coding: c.501C>T
MANE Select: NM_000146
dbSNP: rs759937926
Type: single nucleotide variant
Location: chr19:48966708 (GRCh38)
Gene constraint: LOEUF 1.552 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 96.69 · 17 PDB
Residue 167: an α-helix

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

Disease context

hereditary hyperferritinemia with congenital cataracts — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neuroferritinopathy

For Hereditary hyperferritinemia-cataract syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages

Similar variants

FTL p.Phe167fs Pathogenic same residue
FTL c.-149G>C Pathogenic/Likely pathogenic ★★ same condition
FTL c.-150C>A Pathogenic/Likely pathogenic ★★ same condition
FTL c.-157G>A Pathogenic/Likely pathogenic ★★ same condition
FTL c.-160A>G Pathogenic ★★ same condition
FTL c.-161C>T Pathogenic/Likely pathogenic ★★ same condition
FTL c.-164C>A Pathogenic/Likely pathogenic ★★ same condition
FTL c.-167C>T Pathogenic ★★ same condition

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/ftl-p-phe167 (accessed [today's date]).

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