Is CP p.Thr313Ile (c.938C>T) pathogenic?

CP p.Thr313Ile (c.938C>T) is classified Conflicting classifications of pathogenicity in CP (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-01-25). AlphaMissense: likely benign (0.2045); Ultra-rare (popmax 0.0743%, nfe); Associated with aceruloplasminemia.

What condition is associated with CP p.Thr313Ile (c.938C>T)?

CP p.Thr313Ile (c.938C>T) is associated with aceruloplasminemia (ClinVar).

How common is CP p.Thr313Ile (c.938C>T) in the general population?

CP p.Thr313Ile (c.938C>T) is ultra-rare (popmax 0.0743%, nfe) (gnomAD).

How is Aceruloplasminemia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CP p.Thr313Ile (c.938C>T)?

AlphaMissense predicts likely benign (score 0.2045) — an in-silico prediction, not a clinical call.

CP p.Thr313Ile

c.938C>T · rs144401501 · VCV343779

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.2045 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0743%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

aceruloplasminemia

Computational evidence

Protein change
AlphaMissense	0.2045	likely benign
REVEL	0.641	indeterminate
SaProt	LLR -9.88	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.63 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.7	GERP 0.43, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 23 kb · p 0.56 · regional, not allelic
Overall
CADD	21.4	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 0.0743% European (non-Finnish) · 877/1,179,886 alleles

Filtering AF 0.0702% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0685%

Overall 0.0584% 942/1,613,872 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0743%	1,345
Remaining individualsnot grpmax-eligible	0.0528%	1,893
Finnishnot grpmax-eligible	0.0187%	5,336
African / African-American	0.016%	6,243
Admixed American	0.0117%	8,571
South Asian	0.0011%	91,086

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: CP
Protein: p.Thr313Ile
Coding: c.938C>T
MANE Select: NM_000096
dbSNP: rs144401501
Type: single nucleotide variant
Location: chr3:149207461 (GRCh38)
Gene constraint: LOEUF 0.624 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.79 · 4 PDB
Residue 313: the plastocyanin-like 2 domain; a disulfide bond

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

Disease context

aceruloplasminemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Aceruloplasminemia (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult, Elderly
Prevalence: 1-9 / 1 000 000 (Japan)

Similar variants

CP c.1208+1G>A Pathogenic ★★ same condition
CP c.2879-1G>T Likely pathogenic ★★ same condition
CP p.Arg901Ter Pathogenic ★★ same condition
CP p.Gly195Arg Likely pathogenic ★★ same condition
CP p.Gly650Arg Pathogenic/Likely pathogenic ★★ same condition
CP p.Gly708Ser Pathogenic ★★ same condition
CP p.Leu919Pro Pathogenic/Likely pathogenic ★★ same condition
CP p.Val219Glu Likely pathogenic ★★ 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/cp-p-thr313ile (accessed [today's date]).

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