Is CHD1 p.Phe86Val (c.256T>G) pathogenic?

CHD1 p.Phe86Val (c.256T>G) is classified Uncertain significance in CHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-26). AlphaMissense: ambiguous (0.3796); Ultra-rare (popmax 0.0166%, mid).

How common is CHD1 p.Phe86Val (c.256T>G) in the general population?

CHD1 p.Phe86Val (c.256T>G) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about CHD1 p.Phe86Val (c.256T>G)?

AlphaMissense predicts ambiguous (score 0.3796) — an in-silico prediction, not a clinical call.

CHD1 p.Phe86Val

c.256T>G · VCV4227711

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3796 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3796	ambiguous
REVEL	0.67	pathogenic-leaning
SaProt	LLR -5.34	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 26 kb · p 0.65 · regional, not allelic
Overall
CADD	24.4	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

Grpmax group 0.0166% Middle Eastern · 1/6,020 alleles

Filtering AF 0.000708% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000554%

Overall 0.00108% 17/1,567,210 alleles · ultra-rare exomes 15/1,415,032 · genomes 2/152,178 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,020
Remaining individualsnot grpmax-eligible	0.0033%	30,322
European (non-Finnish)	0.00122%	81,956

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: CHD1
Protein: p.Phe86Val
Coding: c.256T>G
MANE Select: NM_001270
Type: single nucleotide variant
Location: chr5:98903908 (GRCh38)
Gene constraint: LOEUF 0.207 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.63 · 18 PDB
Residue 86: the 'disordered' region

Full CHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHD1 p.Arg1378Gly Uncertain significance ★★ ⚠ same type
CHD1 p.Arg1659Thr Uncertain significance ★★ ⚠ same type
CHD1 p.Arg1676Gly Uncertain significance ★★ ⚠ same type
CHD1 p.Arg1708Gln Uncertain significance ★★ same type
CHD1 p.Arg1708Trp Uncertain significance ★★ ⚠ same type
CHD1 p.Arg233His Uncertain significance ★★ same type
CHD1 p.Arg70Ter Uncertain significance ★★ same type
CHD1 p.Asn1518His 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/chd1-p-phe86val (accessed [today's date]).

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