Is DLEU7 p.Phe103Leu (c.309C>A) pathogenic?

DLEU7 p.Phe103Leu (c.309C>A) is classified Uncertain significance in DLEU7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-20). AlphaMissense: ambiguous (0.5163); Ultra-rare (popmax 0.0445%, sas).

How common is DLEU7 p.Phe103Leu (c.309C>A) in the general population?

DLEU7 p.Phe103Leu (c.309C>A) is ultra-rare (popmax 0.0445%, sas) (gnomAD).

What do computational predictors say about DLEU7 p.Phe103Leu (c.309C>A)?

AlphaMissense predicts ambiguous (score 0.5163) — an in-silico prediction, not a clinical call.

DLEU7 p.Phe103Leu

c.309C>A · rs747374364 · VCV3082750

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5163 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0445%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5163	ambiguous
REVEL	0.015	strongly benign-leaning
SaProt	LLR -3.88	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.59	GERP -8.7, phastCons 0.007
Regional constraint	o/e 0.98	unconstrained · MANE · 20 kb · p 0.7 · regional, not allelic
Overall
CADD	0.026	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 0.0445% South Asian · 33/74,126 alleles

Filtering AF 0.0325% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0284%

Overall 0.00257% 38/1,476,046 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0445%	2,246
Middle Eastern	0.0237%	4,228
Remaining individualsnot grpmax-eligible	0.00355%	28,133
Admixed American	0.00241%	41,450
European (non-Finnish)	8.97e-05%	1,114,823

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: DLEU7
Protein: p.Phe103Leu
Coding: c.309C>A
MANE Select: NM_001306135
dbSNP: rs747374364
Type: single nucleotide variant
Location: chr13:50843338 (GRCh38)
Gene constraint: LOEUF 1.902 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.45

Full DLEU7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLEU7 p.Ala2Val Uncertain significance ★ ⚠ same type
DLEU7 p.Ala49Thr Uncertain significance ★ ⚠ same type
DLEU7 p.Ala51Thr Uncertain significance ★ ⚠ same type
DLEU7 p.Ala80Thr Uncertain significance ★ ⚠ same type
DLEU7 p.Ala83Pro Uncertain significance ★ ⚠ same type
DLEU7 p.Ala9Ser Uncertain significance ★ ⚠ same type
DLEU7 p.Arg123Gly Uncertain significance ★ ⚠ same type
DLEU7 p.Arg52Ser 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/dleu7-p-phe103leu (accessed [today's date]).

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