Is CHFR p.Gln14His (c.42G>C) pathogenic?

CHFR p.Gln14His (c.42G>C) is classified Uncertain significance in CHFR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-19). AlphaMissense: likely benign (0.1578); Absent from gnomAD v4.1.

How common is CHFR p.Gln14His (c.42G>C) in the general population?

CHFR p.Gln14His (c.42G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHFR p.Gln14His (c.42G>C)?

AlphaMissense predicts likely benign (score 0.1578) — an in-silico prediction, not a clinical call.

CHFR p.Gln14His

c.42G>C · rs1184750358 · VCV2272358

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1578 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1578	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -8.46	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 -0.24	GERP -0.94, phastCons 0.013
Regional constraint	o/e 0.99	unconstrained · MANE · 34 kb · p 0.86 · regional, not allelic
Overall
CADD	19.99	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHFR
Protein: p.Gln14His
Coding: c.42G>C
MANE Select: NM_001161346
dbSNP: rs1184750358
Type: single nucleotide variant
Location: chr12:132887287 (GRCh38)
Gene constraint: LOEUF 0.929 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.22 · 6 PDB
Residue 14: the 'disordered' region

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

Similar variants

CHFR p.Leu472= Benign ★★ same type
CHFR p.Gln411Ter Likely pathogenic ★ same type
CHFR p.Ala279Val Uncertain significance ★ ⚠ same type
CHFR p.Ala280Ser Uncertain significance ★ ⚠ same type
CHFR p.Ala499Val Uncertain significance ★ ⚠ same type
CHFR p.Ala569Val Uncertain significance ★ ⚠ same type
CHFR p.Arg21His Uncertain significance ★ ⚠ same type
CHFR p.Arg266Gly 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/chfr-p-gln14his (accessed [today's date]).

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