Is C8G p.Arg69Gln (c.206G>A) pathogenic?

C8G p.Arg69Gln (c.206G>A) is classified Benign in C8G (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-20). AlphaMissense: likely benign (0.0812); Low-frequency (popmax 4.83%, afr).

How common is C8G p.Arg69Gln (c.206G>A) in the general population?

C8G p.Arg69Gln (c.206G>A) is low-frequency (popmax 4.83%, afr) (gnomAD).

What do computational predictors say about C8G p.Arg69Gln (c.206G>A)?

AlphaMissense predicts likely benign (score 0.0812) — an in-silico prediction, not a clinical call.

C8G p.Arg69Gln

c.206G>A · rs17614 · VCV769761

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0812 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.83%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0812	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -6.70	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.43	GERP -2.7
Regional constraint	o/e 1.12	unconstrained · MANE · 1,457 bp · p 0.046 · regional, not allelic
Overall
CADD	12.99	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.83% African / African-American · 3,609/74,740 alleles

Filtering AF 4.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.64%

Overall 0.275% 4,393/1,594,644 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.83%	21
Admixed American	0.429%	233
Ashkenazi Jewishnot grpmax-eligible	0.382%	262
Remaining individualsnot grpmax-eligible	0.366%	274
Middle Eastern	0.322%	310
European (non-Finnish)	0.0145%	6,900
South Asian	0.00901%	11,104
East Asian	0.00226%	44,152

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: C8G
Protein: p.Arg69Gln
Coding: c.206G>A
MANE Select: NM_000606
dbSNP: rs17614
Type: single nucleotide variant
Location: chr9:136945701 (GRCh38)
Gene constraint: LOEUF 1.809 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.06 · 15 PDB
Residue 69: an α-helix; a UniProt-annotated variant site (in)

Full C8G gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C8G p.Arg69Trp Uncertain significance ★ ⚠ same residue
C8G p.Tyr181His Uncertain significance ★★ ⚠ same type
C8G c.276-3C>T Likely benign ★★ same type
C8G p.Val196Ile Likely benign ★★ same type
C8G p.Ala128Thr Uncertain significance ★ ⚠ same type
C8G p.Ala136Thr Uncertain significance ★ ⚠ same type
C8G p.Ala143Val Uncertain significance ★ ⚠ same type
C8G p.Ala16Val 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/c8g-p-arg69gln (accessed [today's date]).

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