Is CHFR p.Ala569Val (c.1706C>T) pathogenic?

CHFR p.Ala569Val (c.1706C>T) is classified Uncertain significance in CHFR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-07). AlphaMissense: likely benign (0.3012); Ultra-rare (popmax 0.098%, eas).

How common is CHFR p.Ala569Val (c.1706C>T) in the general population?

CHFR p.Ala569Val (c.1706C>T) is ultra-rare (popmax 0.098%, eas) (gnomAD).

What do computational predictors say about CHFR p.Ala569Val (c.1706C>T)?

AlphaMissense predicts likely benign (score 0.3012) — an in-silico prediction, not a clinical call.

CHFR p.Ala569Val

c.1706C>T · rs781614371 · VCV3144305

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3012 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.098%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3012	likely benign
REVEL	0.225	benign-leaning
SaProt	LLR -8.90	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 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 12 kb · p 7.1e-05 · regional, not allelic
Overall
CADD	24.5	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A581V vs ClinVar A569V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.098% East Asian · 44/44,876 alleles

Filtering AF 0.075% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0669%

Overall 0.00297% 48/1,613,656 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.098%	1,020
Remaining individualsnot grpmax-eligible	0.0032%	31,228
South Asian	0.0011%	91,080
European (non-Finnish)	8.48e-05%	1,179,807

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: CHFR
Protein: p.Ala569Val
Coding: c.1706C>T
MANE Select: NM_001161346
dbSNP: rs781614371
Type: single nucleotide variant
Location: chr12:132847072 (GRCh38)
Gene constraint: LOEUF 0.929 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.22 · 6 PDB

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.Arg21His Uncertain significance ★ ⚠ same type
CHFR p.Arg266Gly Uncertain significance ★ ⚠ same type
CHFR p.Arg266His 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-ala569val (accessed [today's date]).

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