Is C7 p.Thr598Ser (c.1792A>T) pathogenic?

C7 p.Thr598Ser (c.1792A>T) is classified Benign/Likely benign in C7 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0721); Common (popmax 15.9%, nfe) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about C7 p.Thr598Ser (c.1792A>T)?

AlphaMissense predicts likely benign (score 0.0721) — an in-silico prediction, not a clinical call.

C7 p.Thr598Ser

Q: How common is C7 p.Thr598Ser (c.1792A>T) in the general population?

C7 p.Thr598Ser (c.1792A>T) is common (popmax 15.9%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1792A>T · rs60714178 · VCV1167575

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0721 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 15.9%, nfe) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0721	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -4.55	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 0.35	GERP -3.3
Overall
CADD	10.55	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 15.9% European (non-Finnish) · 187,352/1,178,414 alleles

Filtering AF 15.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 15.8%

Overall 14% 225,024/1,612,242 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	18.5%	5
Finnishnot grpmax-eligible	17.5%	6
European (non-Finnish)grpmax	15.9%	6
Ashkenazi Jewishnot grpmax-eligible	13.2%	8
Remaining individualsnot grpmax-eligible	12.7%	8
Middle Eastern	12.6%	8
Admixed American	7.64%	13
South Asian	6.28%	16
African / African-American	4.58%	22
East Asian	0.0624%	1,603

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Thr598Ser
Coding: c.1792A>T
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs60714178
Type: single nucleotide variant
Location: chr5:40964783 (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 c.281-1G>T Pathogenic/Likely pathogenic ★★ same type
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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
C7 p.Trp205Ter Pathogenic/Likely pathogenic ★★ same type
C7 p.Ala359Thr 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/c7-p-thr598ser (accessed [today's date]).

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