Is C2 c.1902+6G>C pathogenic?

C2 c.1902+6G>C is classified Benign/Likely benign in C2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). Common (popmax 11.8%, sas) — too common for a highly-penetrant pathogenic allele; Associated with age related macular degeneration 14.

What condition is associated with C2 c.1902+6G>C?

C2 c.1902+6G>C is associated with age related macular degeneration 14 (ClinVar).

C2 c.1902+6G>C

Q: How common is C2 c.1902+6G>C in the general population?

C2 c.1902+6G>C is common (popmax 11.8%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs9332730 · VCV356256

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 11.8%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

age related macular degeneration 14

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +6	donor splice region (+6, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.38	GERP 0.074, phastCons 0.006
Non-coding constraint	Z 5.15	1 kb window · o/e 0.65 · regional · uncalibrated
Overall
CADD	11.86	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 11.8% South Asian · 10,679/90,716 alleles

Filtering AF 11.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.5%

Overall 4.95% 79,015/1,595,440 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	14.3%	7
South Asiangrpmax	11.8%	8
Amishnot grpmax-eligible	8.57%	12
Middle Eastern	7.76%	13
European (non-Finnish)	4.51%	22
Remaining individualsnot grpmax-eligible	4.01%	25
African / African-American	2.55%	39
Admixed American	2.43%	41
Ashkenazi Jewishnot grpmax-eligible	0.946%	106
East Asian	0.377%	265

Finnish 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: C2
Coding: c.1902+6G>C
MANE Select: NM_000063
dbSNP: rs9332730
Type: single nucleotide variant
Location: chr6:31944232 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.61 · 14 PDB

Full C2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

age related macular degeneration 14 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

C2 c.1902+5G>A Uncertain significance ★★ same condition
C2 p.Arg129His Uncertain significance ★★ ⚠ same condition
C2 p.Arg734Leu Uncertain significance ★★ ⚠ same condition
C2 p.Asp390Ala Uncertain significance ★★ ⚠ same condition
C2 p.Asp661Asn Uncertain significance ★★ ⚠ same condition
C2 p.Lys572Asn Uncertain significance ★★ ⚠ same condition
C2 p.Phe273= Uncertain significance ★★ same condition
C2 p.Phe95Val Uncertain significance ★★ ⚠ 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/c2-c-1902-plus-6g-c (accessed [today's date]).

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