Is C7 p.Thr587Pro (c.1759A>C) pathogenic?

C7 p.Thr587Pro (c.1759A>C) is classified Benign/Likely benign in C7 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0658); Common (popmax 37.4%, sas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about C7 p.Thr587Pro (c.1759A>C)?

AlphaMissense predicts likely benign (score 0.0658) — an in-silico prediction, not a clinical call.

C7 p.Thr587Pro

Q: How common is C7 p.Thr587Pro (c.1759A>C) in the general population?

C7 p.Thr587Pro (c.1759A>C) is common (popmax 37.4%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1759A>C · rs13157656 · VCV1169276

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0658 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 37.4%, sas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0658	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -3.23	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 -0.93	GERP -5.9
Overall
CADD	1.22	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 37.4% South Asian · 34,002/90,912 alleles

Filtering AF 37.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 36.9%

Overall 23.5% 378,522/1,611,870 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	37.4%	3
Ashkenazi Jewishnot grpmax-eligible	24.4%	4
East Asian	24.1%	4
Remaining individualsnot grpmax-eligible	23.6%	4
European (non-Finnish)	23.6%	4
Finnishnot grpmax-eligible	23.5%	4
Middle Eastern	22.9%	4
Admixed American	22.1%	5
Amishnot grpmax-eligible	12.3%	8
African / African-American	5.9%	17

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.Thr587Pro
Coding: c.1759A>C
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs13157656
Type: single nucleotide variant
Location: chr5:40964750 (GRCh38)
Structure: AlphaFold pLDDT 89.67 · 6 PDB

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

Similar variants

C7 p.Thr587Lys Uncertain significance ★ ⚠ same residue
C7 p.Thr587= Likely benign ★ same residue
C7 c.281-1G>T Pathogenic/Likely pathogenic ★★ same type
C7 c.63-1G>A Pathogenic ★★ same type
C7 c.739-2A>G Likely pathogenic ★★ same type
C7 p.Arg402Ter Pathogenic/Likely pathogenic ★★ same type
C7 p.Gln271Ter Pathogenic/Likely pathogenic ★★ same type
C7 p.Gly379Arg Pathogenic/Likely pathogenic ★★ ⚠ 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/c7-p-thr587pro (accessed [today's date]).

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