Is C8A p.Arg207Gln (c.620G>A) pathogenic?

C8A p.Arg207Gln (c.620G>A) is classified Uncertain significance in C8A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-06-29). AlphaMissense: likely benign (0.2881); Ultra-rare (popmax 0.0168%, mid).

How common is C8A p.Arg207Gln (c.620G>A) in the general population?

C8A p.Arg207Gln (c.620G>A) is ultra-rare (popmax 0.0168%, mid) (gnomAD).

What do computational predictors say about C8A p.Arg207Gln (c.620G>A)?

AlphaMissense predicts likely benign (score 0.2881) — an in-silico prediction, not a clinical call.

C8A p.Arg207Gln

c.620G>A · rs1007715803 · VCV1924287

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2881 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0168%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2881	likely benign
REVEL	0.86	moderately pathogenic-leaning
SaProt	LLR -10.96	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 1.9, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 63 kb · p 0.034 · regional, not allelic
Overall
CADD	29.3	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 0.0168% Middle Eastern · 1/5,942 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000744% 12/1,613,468 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0168%	5,942
East Asian	0.00446%	22,438
Remaining individualsnot grpmax-eligible	0.0032%	31,226
Admixed American	0.00167%	59,970
European (non-Finnish)	0.000509%	196,623

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: C8A
Protein: p.Arg207Gln
Coding: c.620G>A
MANE Select: NM_000562
dbSNP: rs1007715803
Type: single nucleotide variant
Location: chr1:56881600 (GRCh38)
Gene constraint: LOEUF 1.168 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.58 · 11 PDB
Residue 207: a β-strand; the macpf domain

Full C8A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C8A p.Arg207Trp Uncertain significance ★ ⚠ same residue
C8A p.Arg424Ter Pathogenic ★★ same type
C8A p.Arg498Ter Pathogenic/Likely pathogenic ★★ same type
C8A p.Glu466Ter Pathogenic ★★ same type
C8A p.Tyr210Ter Pathogenic/Likely pathogenic ★★ same type
C8A p.Tyr384Ter Pathogenic/Likely pathogenic ★★ same type
C8A p.Arg107Cys Uncertain significance ★★ ⚠ same type
C8A p.Arg196His 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/c8a-p-arg207gln (accessed [today's date]).

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