Is TYR p.Pro38= (c.114G>A) pathogenic?

TYR p.Pro38= (c.114G>A) is classified Benign/Likely benign in TYR (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-31). Common (popmax 5.14%, afr) — too common for a highly-penetrant pathogenic allele; Associated with oculocutaneous albinism.

What condition is associated with TYR p.Pro38= (c.114G>A)?

TYR p.Pro38= (c.114G>A) is associated with oculocutaneous albinism (ClinVar).

TYR p.Pro38=

Q: How common is TYR p.Pro38= (c.114G>A) in the general population?

TYR p.Pro38= (c.114G>A) is common (popmax 5.14%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.114G>A · rs1939261 · VCV255956

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 5.14%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

oculocutaneous albinism

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 -5.8	GERP -3.8
Overall
CADD	0.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.14% African / African-American · 3,856/75,044 alleles

Filtering AF 5% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.95%

Overall 0.28% 4,522/1,614,160 alleles · common exomes 2,365/1,461,858 · genomes 2,157/152,302 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.14%	19
Remaining individualsnot grpmax-eligible	0.315%	317
Admixed American	0.267%	375
Middle Eastern	0.264%	379
Ashkenazi Jewishnot grpmax-eligible	0.105%	955
European (non-Finnish)	0.0209%	4,777
South Asian	0.0154%	6,506
East Asian	0.00223%	44,870

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.Pro38=
Coding: c.114G>A
MANE Select: NM_000372
dbSNP: rs1939261
Type: single nucleotide variant
Location: chr11:89178067 (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

oculocutaneous albinism — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TYR p.Pro38Leu Uncertain significance ★★ ⚠ same residue
TYR p.Pro38Ala Uncertain significance ★ ⚠ same residue
TYR p.Pro38Thr Uncertain significance ★ ⚠ same residue
TYR c.1037-2A>G Pathogenic/Likely pathogenic ★★ same condition
TYR c.1037-7T>A Pathogenic/Likely pathogenic ★★ same condition
TYR p.Ala490Asp Likely pathogenic ★★ same condition
TYR p.Arg116Ter Pathogenic/Likely pathogenic ★★ same condition
TYR p.Arg217Gln Pathogenic/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-pro38 (accessed [today's date]).

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