Is FANCD2 p.Ser338Arg (c.1014C>G) pathogenic?

FANCD2 p.Ser338Arg (c.1014C>G) is classified Uncertain significance in FANCD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-19). AlphaMissense: likely benign (0.1949); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with FANCD2 p.Ser338Arg (c.1014C>G)?

FANCD2 p.Ser338Arg (c.1014C>G) is associated with Inborn genetic diseases (ClinVar).

How common is FANCD2 p.Ser338Arg (c.1014C>G) in the general population?

FANCD2 p.Ser338Arg (c.1014C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FANCD2 p.Ser338Arg (c.1014C>G)?

AlphaMissense predicts likely benign (score 0.1949) — an in-silico prediction, not a clinical call.

FANCD2 p.Ser338Arg

c.1014C>G · rs527769128 · VCV3092791

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1949 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1949	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -8.39	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.44	acceptor loss, 24 bp away · masked 0 · deltas
Pangolin	Δ0.52	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -5	GERP -3.1
Regional constraint	o/e 1.03	unconstrained · MANE · 15 kb · p 0.52 · regional, not allelic
Overall
CADD	14.21	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: FANCD2
Protein: p.Ser338Arg
Coding: c.1014C>G
MANE Select: NM_001018115
dbSNP: rs527769128
Type: single nucleotide variant
Location: chr3:10043508 (GRCh38)
Gene constraint: LOEUF 0.777 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.24 · 13 PDB
Residue 338: the 'interaction with brca2' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FANCD2 p.Ser338= Likely benign ★ same residue
FANCD2 p.Ala329Pro Uncertain significance ★★ ⚠ same condition
FANCD2 p.Arg315Gln Uncertain significance ★★ ⚠ same condition
FANCD2 p.Asn1213Lys Uncertain significance ★★ ⚠ same condition
FANCD2 p.Asn601Ser Uncertain significance ★★ ⚠ same condition
FANCD2 p.Cys342Tyr Uncertain significance ★★ ⚠ same condition
FANCD2 p.Cys657Ser Uncertain significance ★★ ⚠ same condition
FANCD2 p.Gln308Arg Uncertain significance ★★ ⚠ same condition

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-ser338arg (accessed [today's date]).

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