Is CNTFR p.Ala313Ser (c.937G>T) pathogenic?

CNTFR p.Ala313Ser (c.937G>T) is classified Uncertain significance in CNTFR (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-10). AlphaMissense: likely benign (0.0844); Ultra-rare (popmax 0.0681%, afr).

How common is CNTFR p.Ala313Ser (c.937G>T) in the general population?

CNTFR p.Ala313Ser (c.937G>T) is ultra-rare (popmax 0.0681%, afr) (gnomAD).

What do computational predictors say about CNTFR p.Ala313Ser (c.937G>T)?

AlphaMissense predicts likely benign (score 0.0844) — an in-silico prediction, not a clinical call.

CNTFR p.Ala313Ser

c.937G>T · rs148059931 · VCV2211598

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0844 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0681%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0844	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -6.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 540 bp · p 0.24 · regional, not allelic
Overall
CADD	20.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0681% African / African-American · 51/74,904 alleles

Filtering AF 0.0532% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0479%

Overall 0.00384% 62/1,613,158 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0681%	1,469
Middle Eastern	0.0164%	6,080
Remaining individualsnot grpmax-eligible	0.00801%	12,492
Admixed American	0.00667%	14,993
South Asian	0.0011%	91,072

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: CNTFR
Protein: p.Ala313Ser
Coding: c.937G>T
MANE Select: NM_147164
dbSNP: rs148059931
Type: single nucleotide variant
Location: chr9:34552686 (GRCh38)
Gene constraint: LOEUF 0.547 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 84.12 · 5 PDB
Residue 313: the 'disordered' region

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.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
CNTFR p.Arg167Cys 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-ala313ser (accessed [today's date]).

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