Is DDHD1 p.Phe41Leu (c.123C>A) pathogenic?

DDHD1 p.Phe41Leu (c.123C>A) is classified Uncertain significance in DDHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: ambiguous (0.3982); No allele count reported in gnomAD v4.1 (AN 1,571,412); Associated with Inborn genetic diseases.

What condition is associated with DDHD1 p.Phe41Leu (c.123C>A)?

DDHD1 p.Phe41Leu (c.123C>A) is associated with Inborn genetic diseases (ClinVar).

How common is DDHD1 p.Phe41Leu (c.123C>A) in the general population?

DDHD1 p.Phe41Leu (c.123C>A) is no allele count reported in gnomAD v4.1 (AN 1,571,412) (gnomAD).

What do computational predictors say about DDHD1 p.Phe41Leu (c.123C>A)?

AlphaMissense predicts ambiguous (score 0.3982) — an in-silico prediction, not a clinical call.

DDHD1 p.Phe41Leu

c.123C>A · VCV4238372

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3982 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,571,412)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3982	ambiguous
REVEL	0.012	strongly benign-leaning
SaProt	LLR -4.67	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.55	GERP 0.45, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 825 bp · p 0.0075 · regional, not allelic
Overall
CADD	17.21	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

No allele count reported in gnomAD v4.1 (AN 1,571,412). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DDHD1
Protein: p.Phe41Leu
Coding: c.123C>A
MANE Select: NM_001160148
Type: single nucleotide variant
Location: chr14:53152976 (GRCh38)
Gene constraint: LOEUF 0.642 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 67.11

Full DDHD1 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

DDHD1 p.Phe41Cys Uncertain significance ★ ⚠ same residue
DDHD1 p.Ala94Pro Uncertain significance ★★ ⚠ same condition
DDHD1 p.Arg204Trp Uncertain significance ★★ ⚠ same condition
DDHD1 p.Arg570Gln Uncertain significance ★★ ⚠ same condition
DDHD1 p.Arg588Gln Uncertain significance ★★ ⚠ same condition
DDHD1 p.Arg596Gln Uncertain significance ★★ ⚠ same condition
DDHD1 p.Arg732His Uncertain significance ★★ ⚠ same condition
DDHD1 p.Asn279Ser 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/ddhd1-p-phe41leu (accessed [today's date]).

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