Is CFTR p.Gly1237= (c.3711C>T) pathogenic?

CFTR p.Gly1237= (c.3711C>T) is classified Uncertain significance in CFTR (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-25). Very rare (popmax 0.00267%, afr).

How common is CFTR p.Gly1237= (c.3711C>T) in the general population?

CFTR p.Gly1237= (c.3711C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

CFTR p.Gly1237=

c.3711C>T · rs1316425599 · VCV1163012

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.017	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.48	GERP -2.2, phastCons 0.016
Overall
CADD	6.496	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,954 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,610,816 alleles · very rare exomes 3/1,458,644 · genomes 0/152,172 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,477
European (non-Finnish)	8.48e-05%	1,179,284

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: CFTR
Protein: p.Gly1237=
Coding: c.3711C>T
MANE Select: NM_000492
dbSNP: rs1316425599
Type: single nucleotide variant
Location: chr7:117627764 (GRCh38)
Gene constraint: LOEUF 1.152 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 60 PDB
Residue 1237: a UniProt-annotated variant site (in cf); the abc transporter 2 domain

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

Similar variants

CFTR p.Gly1237Asp Uncertain significance ★★ ⚠ same residue
CFTR p.Gly1237Ser Uncertain significance ★ ⚠ same residue
CFTR c.1585-1G>A Pathogenic ★★★★ same type
CFTR c.1766+1G>A Pathogenic ★★★★ same type
CFTR c.2657+5G>A Pathogenic ★★★★ same type
CFTR c.2988+1G>A Pathogenic ★★★★ same type
CFTR c.3718-2477C>T Pathogenic ★★★★ same type
CFTR c.489+1G>T Pathogenic ★★★★ 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/cftr-p-gly1237 (accessed [today's date]).

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