Is GC p.Lys229= (c.687G>A) pathogenic?

GC p.Lys229= (c.687G>A) is classified Likely benign in GC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-08-01). Rare (popmax 0.2%, mid).

How common is GC p.Lys229= (c.687G>A) in the general population?

GC p.Lys229= (c.687G>A) is rare (popmax 0.2%, mid) (gnomAD).

GC p.Lys229=

c.687G>A · rs111261486 · VCV773155

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.2%, mid)

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 -0.36	phastCons 0.084
Overall
CADD	5.705	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.2% Middle Eastern · 12/5,994 alleles

Filtering AF 0.156% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.146%

Overall 0.128% 2,020/1,584,002 alleles · rare exomes 1,823/1,431,710 · genomes 197/152,292 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.709%	141
Middle Easterngrpmax	0.2%	500
Admixed American	0.184%	544
Remaining individualsnot grpmax-eligible	0.171%	585
European (non-Finnish)	0.135%	741
Amishnot grpmax-eligible	0.11%	912
African / African-American	0.0269%	3,720
South Asian	0.00775%	12,904
Finnishnot grpmax-eligible	0.00157%	63,862

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys229=
Coding: c.687G>A
MANE Select: NM_000583
dbSNP: rs111261486
Type: single nucleotide variant
Location: chr4:71763422 (GRCh38)
Gene constraint: LOEUF 1.492 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.81 · 6 PDB
Residue 229: the albumin 2 domain; an α-helix

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.Lys94= Benign ★★ same type
GC p.Tyr136= 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-lys229 (accessed [today's date]).

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