Is C8A p.Gly571Arg (c.1711G>A) pathogenic?

C8A p.Gly571Arg (c.1711G>A) is classified Uncertain significance in C8A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-08). AlphaMissense: ambiguous (0.5169); Very rare (popmax 0.00267%, afr).

How common is C8A p.Gly571Arg (c.1711G>A) in the general population?

C8A p.Gly571Arg (c.1711G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about C8A p.Gly571Arg (c.1711G>A)?

AlphaMissense predicts ambiguous (score 0.5169) — an in-silico prediction, not a clinical call.

C8A p.Gly571Arg

c.1711G>A · VCV4647342

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5169 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Computational evidence

Protein change
AlphaMissense	0.5169	ambiguous
REVEL	0.606	indeterminate
SaProt	LLR -17.21	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.2, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 63 kb · p 0.034 · regional, not allelic
Overall
CADD	25.9	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 0.00267% African / African-American · 2/74,940 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00031% 5/1,614,092 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,470
European (non-Finnish)	0.000254%	393,348

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.Gly571Arg
Coding: c.1711G>A
MANE Select: NM_000562
Type: single nucleotide variant
Location: chr1:56917672 (GRCh38)
Gene constraint: LOEUF 1.168 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.58 · 11 PDB
Residue 571: an α-helix; the tsp type-1 2 domain; the 'disordered' region; a disulfide bond; a UniProt-annotated variant site (in c8d1)

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

Similar variants

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
C8A p.Arg207Gln 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-gly571arg (accessed [today's date]).

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