Is C2 p.Asn310Ser (c.929A>G) pathogenic?

C2 p.Asn310Ser (c.929A>G) is classified Conflicting classifications of pathogenicity in C2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-11-21). AlphaMissense: likely benign (0.0672); Ultra-rare (popmax 0.0866%, amr); Associated with age related macular degeneration 14.

What condition is associated with C2 p.Asn310Ser (c.929A>G)?

C2 p.Asn310Ser (c.929A>G) is associated with age related macular degeneration 14, complement component 2 deficiency (ClinVar).

How common is C2 p.Asn310Ser (c.929A>G) in the general population?

C2 p.Asn310Ser (c.929A>G) is ultra-rare (popmax 0.0866%, amr) (gnomAD).

What do computational predictors say about C2 p.Asn310Ser (c.929A>G)?

AlphaMissense predicts likely benign (score 0.0672) — an in-silico prediction, not a clinical call.

C2 p.Asn310Ser

c.929A>G · rs144201432 · VCV907958

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0672 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0866%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

age related macular degeneration 14

Computational evidence

Protein change
AlphaMissense	0.0672	likely benign
REVEL	0.147	moderately benign-leaning
SaProt	LLR -6.71	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 -0.31	GERP -2.9
Regional constraint	o/e 0.84	unconstrained · MANE · 18 kb · p 1.1e-06 · regional, not allelic
Overall
CADD	0.411	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 0.0866% Admixed American · 52/60,028 alleles

Filtering AF 0.0678% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0611%

Overall 0.0467% 754/1,613,058 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0866%	1,154
European (non-Finnish)	0.0553%	1,807
Remaining individualsnot grpmax-eligible	0.0416%	2,404
Ashkenazi Jewishnot grpmax-eligible	0.0203%	4,934
Finnishnot grpmax-eligible	0.0159%	6,294
African / African-American	0.00933%	10,719

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: C2
Protein: p.Asn310Ser
Coding: c.929A>G
MANE Select: NM_000063
dbSNP: rs144201432
Type: single nucleotide variant
Location: chr6:31936002 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.61 · 14 PDB
Residue 310: the vwfa domain

Full C2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Also linked: complement component 2 deficiency

Similar variants

C2 p.Asn310= Likely benign ★ same residue
C2 c.1902+5G>A Uncertain significance ★★ same condition
C2 p.Arg129His Uncertain significance ★★ same condition
C2 p.Arg734Leu Uncertain significance ★★ ⚠ same condition
C2 p.Asp390Ala Uncertain significance ★★ ⚠ same condition
C2 p.Asp661Asn Uncertain significance ★★ ⚠ same condition
C2 p.Lys572Asn Uncertain significance ★★ ⚠ same condition
C2 p.Phe273= 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/c2-p-asn310ser (accessed [today's date]).

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