ADH1C p.Phe141=
c.423C>T · rs35725608 · VCV730985
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.283%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.002 | GERP -1.9 |
| Overall | ||
| CADD | 7.6 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.283%
European (non-Finnish) · 3,345/1,180,040 alleles
Filtering AF
0.275%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.272%
Overall
0.222%
3,588/1,614,162 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.283% | 353 |
| Remaining individualsnot grpmax-eligible | 0.24% | 417 |
| Admixed American | 0.08% | 1,251 |
| Middle Eastern | 0.0495% | 2,021 |
| African / African-American | 0.0346% | 2,886 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0135% | 7,402 |
| Finnishnot grpmax-eligible | 0.0125% | 8,004 |
| South Asian | 0.00329% | 30,357 |
| East Asian | 0.00223% | 44,872 |
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
- ADH1C
- Protein
- p.Phe141=
- Coding
- c.423C>T
- MANE Select
- NM_000669
- dbSNP
- rs35725608
- Type
- single nucleotide variant
- Location
- chr4:99345006 (GRCh38)
- Gene constraint
- LOEUF 0.991 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 98.13 · 2 PDB
Similar variants
- ADH1C p.His139Tyr Uncertain significance ★★ ⚠ same type
- ADH1C p.Arg48His Benign ★★ same type
- ADH1C p.Gly143= Benign/Likely benign ★★ same type
- ADH1C p.Gly174= Benign/Likely benign ★★ same type
- ADH1C p.Gly78= Benign ★★ same type
- ADH1C p.Pro352Thr Benign ★★ ⚠ same type
- ADH1C p.Ala164Val Uncertain significance ★ ⚠ same type
- ADH1C p.Arg313His 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/adh1c-p-phe141 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown