Is C7 p.Ala611Pro (c.1831G>C) pathogenic?

C7 p.Ala611Pro (c.1831G>C) is classified Uncertain significance in C7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-27). AlphaMissense: likely pathogenic (0.8188); Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with C7 p.Ala611Pro (c.1831G>C)?

C7 p.Ala611Pro (c.1831G>C) is associated with Inborn genetic diseases (ClinVar).

How common is C7 p.Ala611Pro (c.1831G>C) in the general population?

C7 p.Ala611Pro (c.1831G>C) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about C7 p.Ala611Pro (c.1831G>C)?

AlphaMissense predicts likely pathogenic (score 0.8188) — an in-silico prediction, not a clinical call.

C7 p.Ala611Pro

c.1831G>C · rs752503418 · VCV1912703

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8188 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8188	likely pathogenic · top 7% in C7
REVEL	0.607	indeterminate
SaProt	LLR -14.23	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.9, phastCons 1
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00149% 24/1,613,666 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
Remaining individualsnot grpmax-eligible	0.0048%	20,817
East Asian	0.00223%	44,886
European (non-Finnish)	0.00161%	62,092

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: C7
Protein: p.Ala611Pro
Coding: c.1831G>C
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs752503418
Type: single nucleotide variant
Location: chr5:40964822 (GRCh38)
Structure: AlphaFold pLDDT 89.67 · 6 PDB

Full C7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

C7 p.Ala359Thr Uncertain significance ★★ ⚠ same condition
C7 p.Ala53Val Uncertain significance ★★ ⚠ same condition
C7 p.Ala839Thr Uncertain significance ★★ ⚠ same condition
C7 p.Arg220Trp Uncertain significance ★★ ⚠ same condition
C7 p.Arg226Ile Uncertain significance ★★ ⚠ same condition
C7 p.Arg293Gln Uncertain significance ★★ ⚠ same condition
C7 p.Arg372Gln Uncertain significance ★★ ⚠ same condition
C7 p.Arg402Gln 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/c7-p-ala611pro (accessed [today's date]).

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