Is CNTFR p.Pro122Ser (c.364C>T) pathogenic?

CNTFR p.Pro122Ser (c.364C>T) is classified Uncertain significance in CNTFR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-10). AlphaMissense: likely pathogenic (0.9967); Absent from gnomAD v4.1.

How common is CNTFR p.Pro122Ser (c.364C>T) in the general population?

CNTFR p.Pro122Ser (c.364C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CNTFR p.Pro122Ser (c.364C>T)?

AlphaMissense predicts likely pathogenic (score 0.9967) — an in-silico prediction, not a clinical call.

CNTFR p.Pro122Ser

c.364C>T · VCV3494591

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9967 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,572,388)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9967	likely pathogenic · top 8% in CNTFR
REVEL	0.304	indeterminate
SaProt	LLR -6.17	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 11 kb · p 0.23 · regional, not allelic
Overall
CADD	25.4	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

No allele count reported in gnomAD v4.1 (AN 1,572,388). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CNTFR
Protein: p.Pro122Ser
Coding: c.364C>T
MANE Select: NM_147164
Type: single nucleotide variant
Location: chr9:34557940 (GRCh38)
Gene constraint: LOEUF 0.547 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 84.12 · 5 PDB
Residue 122: a disulfide bond; a β-strand; the fibronectin type-iii 1 domain

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

Similar variants

CNTFR c.438-1G>A Uncertain significance ★ same type
CNTFR p.Ala297Thr Uncertain significance ★ ⚠ same type
CNTFR p.Ala313Ser Uncertain significance ★ ⚠ same type
CNTFR p.Ala316Val Uncertain significance ★ ⚠ same type
CNTFR p.Ala367Thr Uncertain significance ★ ⚠ same type
CNTFR p.Ala3Val Uncertain significance ★ ⚠ same type
CNTFR p.Ala54Val Uncertain significance ★ ⚠ same type
CNTFR p.Ala8Val 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/cntfr-p-pro122ser (accessed [today's date]).

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