Is GC p.Tyr136= (c.408C>T) pathogenic?

GC p.Tyr136= (c.408C>T) is classified Benign in GC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-08-18). Common (popmax 5.19%, afr) — too common for a highly-penetrant pathogenic allele.

GC p.Tyr136=

Q: How common is GC p.Tyr136= (c.408C>T) in the general population?

GC p.Tyr136= (c.408C>T) is common (popmax 5.19%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.408C>T · rs58801122 · VCV784040

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.19%, 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 -9.3	GERP -5.2
Overall
CADD	0.069	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.19% African / African-American · 3,895/74,992 alleles

Filtering AF 5.06% ClinGen BA1/BS1 input FAF95, joint · FAF99 5%

Overall 0.283% 4,562/1,613,940 alleles · common exomes 2,321/1,461,726 · genomes 2,241/152,214 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.19%	19
Remaining individualsnot grpmax-eligible	0.467%	214
Middle Eastern	0.366%	273
Admixed American	0.338%	296
South Asian	0.078%	1,283
East Asian	0.0134%	7,478
European (non-Finnish)	0.00619%	16,164

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: GC
Protein: p.Tyr136=
Coding: c.408C>T
MANE Select: NM_000583
dbSNP: rs58801122
Type: single nucleotide variant
Location: chr4:71765497 (GRCh38)
Gene constraint: LOEUF 1.492 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.81 · 6 PDB
Residue 136: the albumin 1 domain

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

Similar variants

GC c.701+7A>G Likely benign ★★ same type
GC p.Arg425= Benign ★★ same type
GC p.Asn288Asp Benign ★★ same type
GC p.Lys229= Likely benign ★★ same type
GC p.Lys94= Benign ★★ same type
GC p.Ala147Val Uncertain significance ★ ⚠ same type
GC p.Arg218Lys Uncertain significance ★ ⚠ same type
GC p.Asn217His 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/gc-p-tyr136 (accessed [today's date]).

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