Is TYR p.Phe231fs (c.693del) pathogenic?

TYR p.Phe231fs (c.693del) is classified Likely pathogenic in TYR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-10). Very rare (popmax 0.0022%, sas); Associated with SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN.

What condition is associated with TYR p.Phe231fs (c.693del)?

TYR p.Phe231fs (c.693del) is associated with SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN (ClinVar).

How common is TYR p.Phe231fs (c.693del) in the general population?

TYR p.Phe231fs (c.693del) is very rare (popmax 0.0022%, sas) (gnomAD).

TYR p.Phe231fs

c.693del · rs745847253 · VCV3240679

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,034 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000124% 2/1,613,080 alleles · very rare exomes 2/1,460,832 · genomes 0/152,248 · 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: TYR
Protein: p.Phe231fs
Coding: c.693del
MANE Select: NM_000372
dbSNP: rs745847253
Type: Deletion
Location: chr11:89178646 (GRCh38)
Gene constraint: LOEUF 1.346 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.79 · 1 PDB

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

Disease context

SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TYR p.Arg217fs Pathogenic ★★ same condition
TYR p.Gly191fs Pathogenic ★★ same condition
TYR p.His389fs Pathogenic ★★ same condition
TYR p.Leu60fs Pathogenic/Likely pathogenic ★★ same condition
TYR p.Ser192fs Pathogenic ★★ same condition
TYR p.Val393fs Pathogenic/Likely pathogenic ★★ same condition
TYR p.Val74fs Pathogenic/Likely pathogenic ★★ same condition
TYR p.Ala141fs Likely 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/tyr-p-phe231fs (accessed [today's date]).

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