Is C2CD3 p.Ser21Asn (c.62G>A) pathogenic?

C2CD3 p.Ser21Asn (c.62G>A) is classified Benign/Likely benign in C2CD3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-15). AlphaMissense: likely benign (0.2882); Rare (popmax 0.835%, sas).

How common is C2CD3 p.Ser21Asn (c.62G>A) in the general population?

C2CD3 p.Ser21Asn (c.62G>A) is rare (popmax 0.835%, sas) (gnomAD).

What do computational predictors say about C2CD3 p.Ser21Asn (c.62G>A)?

AlphaMissense predicts likely benign (score 0.2882) — an in-silico prediction, not a clinical call.

C2CD3 p.Ser21Asn

c.62G>A · rs570315365 · VCV736404

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2882 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.835%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2882	likely benign
REVEL	0.328	indeterminate
SaProt	LLR -7.82	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 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 157 kb · p 9.8e-06 · regional, not allelic
Overall
CADD	25.0	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 0.835% South Asian · 760/91,028 alleles

Filtering AF 0.786% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.766%

Overall 0.0512% 826/1,613,564 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.835%	120
Remaining individualsnot grpmax-eligible	0.0752%	1,330
African / African-American	0.0107%	9,375
East Asian	0.00446%	22,443
Finnishnot grpmax-eligible	0.00156%	64,000
European (non-Finnish)	0.000678%	147,457

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: C2CD3
Protein: p.Ser21Asn
Coding: c.62G>A
MANE Select: NM_001286577
dbSNP: rs570315365
Type: single nucleotide variant
Location: chr11:74168607 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.65
Residue 21: the 'disordered' region

Full C2CD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C2CD3 c.3911-2A>T Pathogenic/Likely pathogenic ★★ same type
C2CD3 p.Arg621Ter Pathogenic/Likely pathogenic ★★ same type
C2CD3 p.Arg666Ter Pathogenic ★★ same type
C2CD3 p.Arg768Ter Pathogenic/Likely pathogenic ★★ same type
C2CD3 p.Tyr173Ter Pathogenic/Likely pathogenic ★★ same type
C2CD3 c.2085+5G>A Uncertain significance ★★ same type
C2CD3 c.4951+6C>T Uncertain significance ★★ same type
C2CD3 c.5495+4A>G 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/c2cd3-p-ser21asn (accessed [today's date]).

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