Is C7 p.Thr211Met (c.632C>T) pathogenic?

C7 p.Thr211Met (c.632C>T) is classified Uncertain significance in C7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-01). AlphaMissense: likely benign (0.1028); Ultra-rare (popmax 0.0124%, amr); Associated with Inborn genetic diseases.

What condition is associated with C7 p.Thr211Met (c.632C>T)?

C7 p.Thr211Met (c.632C>T) is associated with Inborn genetic diseases (ClinVar).

How common is C7 p.Thr211Met (c.632C>T) in the general population?

C7 p.Thr211Met (c.632C>T) is ultra-rare (popmax 0.0124%, amr) (gnomAD).

What do computational predictors say about C7 p.Thr211Met (c.632C>T)?

AlphaMissense predicts likely benign (score 0.1028) — an in-silico prediction, not a clinical call.

C7 p.Thr211Met

c.632C>T · rs749541097 · VCV1396091

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1028 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0124%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1028	likely benign
REVEL	0.229	benign-leaning
SaProt	LLR -6.30	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.40	acceptor gain · deltas
Pangolin	Δ0.28	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.93	GERP 0.75, phastCons 0.21
Overall
CADD	21.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0124% Admixed American · 7/56,368 alleles

Filtering AF 0.00575% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0041%

Overall 0.000633% 10/1,579,944 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0124%	8,053
South Asian	0.00116%	86,404
European (non-Finnish)	0.000173%	578,972

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.Thr211Met
Coding: c.632C>T
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs749541097
Type: single nucleotide variant
Location: chr5:40945262 (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.Thr211= Likely benign ★★ same residue
C7 p.Ala359Thr Uncertain significance ★★ ⚠ same condition
C7 p.Ala53Val Uncertain significance ★★ ⚠ same condition
C7 p.Ala611Pro 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

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-thr211met (accessed [today's date]).

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