Is CRTAP p.Phe362Ser (c.1085T>C) pathogenic?

CRTAP p.Phe362Ser (c.1085T>C) is classified Uncertain significance in CRTAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-09). AlphaMissense: ambiguous (0.4317); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with CRTAP p.Phe362Ser (c.1085T>C)?

CRTAP p.Phe362Ser (c.1085T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CRTAP p.Phe362Ser (c.1085T>C) in the general population?

CRTAP p.Phe362Ser (c.1085T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CRTAP p.Phe362Ser (c.1085T>C)?

AlphaMissense predicts ambiguous (score 0.4317) — an in-silico prediction, not a clinical call.

CRTAP p.Phe362Ser

c.1085T>C · VCV4007073

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4317 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4317	ambiguous
REVEL	0.202	benign-leaning
SaProt	LLR -6.44	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 1.9, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 28 kb · p 0.00062 · regional, not allelic
Overall
CADD	24.8	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 0.00223% East Asian · 1/44,888 alleles

Overall 6.2e-05% 1/1,612,918 alleles · very rare exomes 0/1,460,670 · genomes 1/152,248 · joint denominator

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: CRTAP
Protein: p.Phe362Ser
Coding: c.1085T>C
MANE Select: NM_006371
Type: single nucleotide variant
Location: chr3:33134198 (GRCh38)
Gene constraint: LOEUF 1.251 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.81 · 6 PDB
Residue 362: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CRTAP p.Ala26Ser Uncertain significance ★★ ⚠ same condition
CRTAP p.Ala318Val Uncertain significance ★★ ⚠ same condition
CRTAP p.Arg121Cys Uncertain significance ★★ ⚠ same condition
CRTAP p.Arg5Ser Uncertain significance ★★ ⚠ same condition
CRTAP p.Arg78His Uncertain significance ★★ ⚠ same condition
CRTAP p.Asn87Lys Uncertain significance ★★ ⚠ same condition
CRTAP p.Asp310Asn Uncertain significance ★★ ⚠ same condition
CRTAP p.Asp53His 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/crtap-p-phe362ser (accessed [today's date]).

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