Is FANCD2 p.Phe386Val (c.1156T>G) pathogenic?

FANCD2 p.Phe386Val (c.1156T>G) is classified Benign/Likely benign in FANCD2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-05-01). AlphaMissense: likely benign (0.1229); Rare (popmax 0.952%, amr); Associated with ovarian cancer.

What condition is associated with FANCD2 p.Phe386Val (c.1156T>G)?

FANCD2 p.Phe386Val (c.1156T>G) is associated with ovarian cancer, Fanconi anemia (ClinVar).

How common is FANCD2 p.Phe386Val (c.1156T>G) in the general population?

FANCD2 p.Phe386Val (c.1156T>G) is rare (popmax 0.952%, amr) (gnomAD).

What do computational predictors say about FANCD2 p.Phe386Val (c.1156T>G)?

AlphaMissense predicts likely benign (score 0.1229) — an in-silico prediction, not a clinical call.

FANCD2 p.Phe386Val

c.1156T>G · rs149125003 · VCV241729

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1229 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.952%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ovarian cancer

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1229	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -9.79	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.088	GERP -3.7, phastCons 0.073
Regional constraint	o/e 0.62	unconstrained · MANE · 5,919 bp · p 5.4e-07 · regional, not allelic
Overall
CADD	13.58	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 0.952% Admixed American · 545/57,258 alleles

Filtering AF 0.886% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.86%

Overall 0.0982% 1,573/1,601,694 alleles · rare exomes 858/1,450,622 · genomes 715/151,072 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.952%	105
Amishnot grpmax-eligible	0.329%	304
Finnishnot grpmax-eligible	0.219%	456
East Asian	0.155%	645
Ashkenazi Jewishnot grpmax-eligible	0.129%	773
Remaining individualsnot grpmax-eligible	0.118%	850
African / African-American	0.06%	1,666
European (non-Finnish)	0.0548%	1,823
South Asian	0.0187%	5,349
Middle Eastern	0.0165%	6,058

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: FANCD2
Protein: p.Phe386Val
Coding: c.1156T>G
MANE Select: NM_001018115
dbSNP: rs149125003
Type: single nucleotide variant
Location: chr3:10046601 (GRCh38)

Full FANCD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Fanconi anemia

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/fancd2-p-phe386val (accessed [today's date]).

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