Is C8A p.Glu320Asp (c.960G>T) pathogenic?

C8A p.Glu320Asp (c.960G>T) is classified Conflicting classifications of pathogenicity in C8A (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.1263); Rare (popmax 0.601%, sas).

How common is C8A p.Glu320Asp (c.960G>T) in the general population?

C8A p.Glu320Asp (c.960G>T) is rare (popmax 0.601%, sas) (gnomAD).

What do computational predictors say about C8A p.Glu320Asp (c.960G>T)?

AlphaMissense predicts likely benign (score 0.1263) — an in-silico prediction, not a clinical call.

C8A p.Glu320Asp

c.960G>T · rs147513844 · VCV773408

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1263 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.601%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1263	likely benign
REVEL	0.349	indeterminate
SaProt	LLR -3.89	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 1.5	GERP -3.8, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 63 kb · p 0.034 · regional, not allelic
Overall
CADD	13.99	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 0.601% South Asian · 547/91,088 alleles

Filtering AF 0.559% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.542%

Overall 0.176% 2,843/1,614,062 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.601%	167
Middle Eastern	0.281%	356
European (non-Finnish)	0.178%	562
Remaining individualsnot grpmax-eligible	0.16%	625
Admixed American	0.08%	1,250
African / African-American	0.028%	3,574
Finnishnot grpmax-eligible	0.0156%	6,402
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604

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: C8A
Protein: p.Glu320Asp
Coding: c.960G>T
MANE Select: NM_000562
dbSNP: rs147513844
Type: single nucleotide variant
Location: chr1:56886031 (GRCh38)
Gene constraint: LOEUF 1.168 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.58 · 11 PDB
Residue 320: the macpf domain

Full C8A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C8A p.Arg424Ter Pathogenic ★★ same type
C8A p.Arg498Ter Pathogenic/Likely pathogenic ★★ same type
C8A p.Glu466Ter Pathogenic ★★ same type
C8A p.Tyr210Ter Pathogenic/Likely pathogenic ★★ same type
C8A p.Tyr384Ter Pathogenic/Likely pathogenic ★★ same type
C8A p.Arg107Cys Uncertain significance ★★ ⚠ same type
C8A p.Arg196His Uncertain significance ★★ ⚠ same type
C8A p.Arg207Gln 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/c8a-p-glu320asp (accessed [today's date]).

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