Is C7 p.Asn145Ser (c.434A>G) pathogenic?

C7 p.Asn145Ser (c.434A>G) is classified Uncertain significance in C7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-19). AlphaMissense: likely benign (0.1087); Very rare (popmax 0.00561%, sas).

How common is C7 p.Asn145Ser (c.434A>G) in the general population?

C7 p.Asn145Ser (c.434A>G) is very rare (popmax 0.00561%, sas) (gnomAD).

What do computational predictors say about C7 p.Asn145Ser (c.434A>G)?

AlphaMissense predicts likely benign (score 0.1087) — an in-silico prediction, not a clinical call.

C7 p.Asn145Ser

c.434A>G · rs776782605 · VCV1463583

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1087 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00561%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1087	likely benign
REVEL	0.386	indeterminate
SaProt	LLR -7.83	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 1.3, phastCons 1
Overall
CADD	21.6	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 0.00561% South Asian · 5/89,200 alleles

Filtering AF 0.00214% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00139%

Overall 0.00237% 38/1,606,668 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0266%	3,754
South Asiangrpmax	0.00561%	17,840
African / African-American	0.00268%	37,301
East Asian	0.00223%	44,752
Remaining individualsnot grpmax-eligible	0.00161%	62,200
European (non-Finnish)	0.00102%	98,098

Finnish 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.Asn145Ser
Coding: c.434A>G
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs776782605
Type: single nucleotide variant
Location: chr5:40937557 (GRCh38)
Structure: AlphaFold pLDDT 89.67 · 6 PDB

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

Similar variants

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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
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-asn145ser (accessed [today's date]).

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